Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CATECHOLAMINES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed2002

Adrenergic regulation of catecholamine secretion from trout (Oncorhynchus mykiss) chromaffin cells.

The interaction between extracellular catecholamines and catecholamine secretion from chromaffin cells was assessed in rainbow trout (Oncorhynchus mykiss) using an in situ saline-perfused posterior cardinal vein preparation. This was accomplished by comparing the effects of adrenergic receptor agonists and antagonists on stimulus-evoked secretion. An acute bolus injection or extended perfusion with saline containing high levels of either noradrenaline or adrenaline did not affect the baseline secretion of catecholamines. However, catecholamine secretion in response to a bolus injection of the general cholinergic receptor agonist carbachol or electrical stimulation of the nerves innervating the chromaffin cells was abolished or reduced respectively, in preparations perfused with saline containing either catecholamine. To characterize the catecholaminergic inhibition of catecholamine release, secretion in response to carbachol and electrical stimulation was compared in preparations perfused with the adrenergic receptor agonists dobutamine (beta(1)), salbutamol (beta(2)), phenylephrine (alpha(1)) or clonidine (alpha(2)). Prior treatment with dobutamine or phenylephrine was without effect on baseline catecholamine secretion or stimulus-evoked secretion. In contrast, pre-treatment with salbutamol significantly inhibited catecholamine secretion in response to carbachol or electrical stimulation. Pre-treatment with clonidine did not affect carbachol-evoked secretion but did reduce catecholamine secretion during electrical stimulation. The significance of this adrenergic mechanism of regulating stimulus-evoked catecholamine secretion was further established using the adrenergic receptor antagonists nadolol (beta) or phentolamine (alpha). Catecholamine secretion in response to cholinergic stimulation was significantly enhanced in preparations perfused with saline containing nadolol. Furthermore, pre-treatment with phentolamine significantly enhanced adrenaline secretion in response to neuronal stimulation. These results suggest that the mechanisms of adrenergic inhibition of catecholamine secretion from trout chromaffin cells include activation of chromaffin cell membrane beta(2)-receptors and presynaptic alpha(2)-adrenergic receptors.

Adrenergic alpha-Antagonists↗
PubMed1994

Sympatho-adrenal secretion in humans: factors governing catecholamine and storage vesicle peptide co-release.

1. In postganglionic sympathetic neurones and adrenal chromaffin cells, catecholamines are co-stored in vesicles with soluble peptides, including chromogranin A (CgA) and neuropeptide Y (NPY), which are subject to exocytotic co-release with catecholamines. 2. Plasma catecholamine, CgA and NPY responses to stimulators and inhibitors of sympatho-adrenal catecholamine storage and release were measured in humans. Short-term, high-intensity dynamic exercise, prolonged low-intensity dynamic exercise, and assumption of the upright posture, in decreasing order of potency, predominantly stimulated noradrenaline (NA) release from sympathetic nerve endings. Only high-intensity exercise elevated CgA and NPY, which did not peak until 2 min after exercise cessation. Stimulated NA correlated with plasma CgA 2 min after exercise, and with NPY 5 min after exercise. 3. Insulin-evoked hypoglycaemia and caffeine ingestion, in decreasing order of potency, predominantly stimulated adrenaline (AD) release from the adrenal medulla. During insulin hypoglycaemia AD and CgA rose, but NPY was unchanged. Neither NPY nor CgA were altered by caffeine. The rise in CgA after intense adrenal medullary stimulation was greater than its rise after intense sympathetic neuronal stimulation (1.4-versus 1.2-fold, respectively). 4. Infusion of tyramine, which disrupts sympathetic neuronal vesicular NA storage, elevated systolic blood pressure and NA, while NPY and CgA were unchanged. After reserpine, another disruptor of neuronal NA storage, NA transiently rose and then fell; NPY and CgA were unaltered. After the non-exocytotic adrenal medullary secretory stimulus glucagon. AD rose while NA, CgA and NPY did not change. After amantadine, an inhibitor of protein endocytosis, both CgA and fibrinogen rose, while NA and NPY remained unaltered. Neither CgA, NPY, nor catecholamines were altered by the catecholamine uptake and catabolism inhibitors desipramine, cortisol, and pargyline. 5. Human sympathetic nerve contained a far higher ratio of NPY to catecholamines than human adrenal medulla, while adrenal medulla contained far more CgA than sympathetic nerve. 6. It is concluded that peptides are differentially co-stored with catecholamines, with greater abundance of CgA in the adrenal medulla and NPY in sympathetic nerve. Activation of catecholamine release from either the adrenal medulla or sympathetic nerves, therefore, results in quite different changes in plasma concentrations of the catecholamine storage vesicle peptides CgA and NPY. Only profound, intense stimulation of chromaffin cells or sympathetic axons measurably perturbs plasma CgA or NPY concentration; lesser degrees of stimulation perturb plasma catecholamines only. Neither CgA nor NPY are released during non-exocytotic catecholamine secretion.

Adrenal Medulla↗
PubMed2003

Pheochromocytoma: rediscovery as a catecholamine-metabolizing tumor.

Catecholamine-producing tumors are rare neoplasms derived mainly from chromaffin cells of the adrenal medulla (pheochromocytomas) or, in about 10% of cases, from paraganglia (paragangliomas). Diagnosis of these tumors relies heavily on measurements of urinary or plasma catecholamines or catecholamine metabolites. The metabolites are usually thought to be produced after release of catecholamines into the bloodstream. This, however, ignores observations of over 40 yr ago that catecholamines are metabolized within pheochromocytoma tumor cells. Development of improved methods for measurement of catecholamine metabolites, in particular, plasma concentrations of free normetanephrine and metanephrine, has reestablished the importance of intratumoral catecholamine metabolism. In patients with pheochromocytoma, over 90% of the elevations in plasma free normetanephrine and metanephrine result from metabolism of catecholamines within pheochromocytoma tumor cells. This process occurs continuously and independently of variations in catecholamine release. As a consequence, measurements of plasma concentrations and urinary outputs of normetanephrine and metanephrine provide more reliable methods for diagnosis of pheochromocytoma than measurements of the parent amines. Rediscovery of the importance of intratumoral catecholamine metabolism is leading to a reevaluation of the procedures used to diagnose pheochromocytoma. This review provides an update on the diagnosis of pheochromocytoma, with emphasis on identifying and correcting relevant misconceptions about catecholamine metabolism.

Adrenal Gland Neoplasms↗
PubMed2006

CCCP enhances catecholamine release from the perfused rat adrenal medulla.

The present study was designed to investigate the effect of carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, on secretion of catecholamines from the isolated perfused model of the rat adrenal gland and to establish the mechanism of its adrenomedullary secretion. The perfusion of CCCP (3x10(-5) M) into an adrenal vein of for 90 min caused a great increase in catecholamine secretion. Tachyphylaxis to catecholamine-releasing effect of CCCP was not observed by repeated perfusion of it. The net catecholamine-releasing effects of CCCP were depressed by pretreament with pirenzepine (a selective muscarinic M(1)-receptor antagonist), chlorisondamine (a selective neuronal nicotinic receptor antagonist), nicardipine (an L-type Ca2+-channel antagonist), TMB-8 (an intracellular Ca2+-antagonist), and the perfusion of EGTA plus Ca2+-free medium, respectively. In the presence of CCCP (3x10(-5) M), catecholamine secretory responses induced by ACh (5.32x10(-3) M), high K+ (5.6x10(-2) M, a direct membrane depolarizer), DMPP (10(-4) M, (a selective neuronal nicotinic receptor agonist), and McN-A-343 (10(-4) M, (a selective muscarinic M1-receptor agonist) were significantly enhanced. CCCP also significantly enhanced the catecholamine secretory responses evoked by Bay-K-8644 (10(-5) M), L-type Ca2+ channel activator, and cyclopiazonic acid (10(-5) M), an inhibitor of Ca2+-ATPase. Furthermore, the perfusion of FCCP (3x10(-5) M), a similar mitochondrial uncoupler, into an adrenal vein of for 90 min also caused a great increase in catecholamine secretion in a similar pattern with CCCP. Taken together, the results demonstrate that CCCP causes the catecholamine secretion from the perfused rat adrenal medulla in a calcium-dependent fashion. It is thought that this catecholamine secretory enhancement of CCCP may be mediated by both cholinergic receptor stimulation and membrane depolarization, which are relevant to the cytoplasmic Ca2+ increase by stimulation of the Ca2+ influx as well as by the inhibition of Ca2+ uptake into the cytoplasmic Ca2+ stores (both endoplasmic reticulum and mitochondria in chromaffin cells). It also seems that protonophores, such as CCCP, suppress mitochondrial Ca2+ uptake and increase the stimulated secretion of catecholamine by the secretagogues. These results indicate that mitochondria modulate catecholamine secretion by regulating the Ca2+ mobilization for exocytosis.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1979

The effect of veratridine on the release of catecholamines from the perfused adrenal gland.

1. Experiments on perfused adrenal glands of guinea-pigs were carried out to study the catecholamine output induced by veratridine in the presence of hexamethonium and atropine. 2. Veratridine (10 micrometer to 200 micrometer) caused a dose-dependent increase in catecholamine output. 3. The addition of veratridine to the perfusion medium for a period of 3 min caused an increase in catecholamine output which reached a maximum 5 min to 10 min after withdrawal of the drug. The catecholamine output then gradually declined and reached near resting values within 30 minutes. It was never sustained for a longer period, even when veratridine was infused for 1 hour. 4. Veratridine failed to increase the catecholamine output in the absence of extracellular Ca2+. However, the addition of Ca2+ after an infusion of veratridine (100 micrometer) in the absence of Ca2+ caused an increase in the catecholamine output which was proportional to the concentration of Ca2+ (0.55 mM to 8.8 mM) used. 5. Veratridine did not increase the catecholamine output in the absence of extracellular Na+ ions, NaCl being replaced by equimolar choline chloride or LiCl. Veratridine also failed to evoke catecholamine output in a Na+-free solution in which Na+ was replaced by sucrose; this was the case even in the presence of a high concentration of Ca2+ (8.8 mM). 6. Tetrodotoxin (0.1 micrometer) and excess Mg2+ (20 mM) reversibly inhibited the catecholamine output induced by veratridine. 7. Ouabain (10 micrometer) significantly potentiated the veratridine-induced catecholamine output. 8. It is suggested that Na+-dependent Ca2+ influx as well as voltage-dependent Ca2+ influx mechanisms may be involved in the catecholamine output induced by veratridine.

Adrenal Glands↗
PubMed1982

Plasma catecholamines, heart rate, and cardiac sympathetic activity in exercising dogs.

Plasma catecholamines, heart rate, and cardiac sympathetic activity in exercising dogs. Med. Sci. Sports Exercise, Vol. 14, No. 4, pp. 291-285, 1982. The purposes of the study were, 1) to assess the respective roles of locally released norepinephrine in the sinus node and of plasma catecholamines in the control of heart rate during exercise and 2) to verify whether the heart is a source of plasma catecholamines during exercise. Plasma catecholamines (radioenzymatic assay) and heart rate were measured in the last minute of a 5-min exercise period (3.2 km . h-1, 39% slope) in six normal dogs, in six dogs treated with 5 mg . kg-1 sotalol, and in six dogs sympathectomized with 50 mg . kg-1 6-hydroxydopamine. Compared to the exercise heart rate values of the normal dogs (228 +/- 8 beats . min-1) and the sympathectomized dogs (226 +/- 9 beats . min-1), the sotalol-treated dogs had significantly lower rates (148 +/- 6 beats . min-1). However, plasma catecholamine response was higher in the sotalol-treated dogs (7380 +/- 1350 pg . ml-1) and in the sympathectomized dogs (4280 +/- 680 pg . ml-1) than in the normal dogs (1890 +/- 360 pg . ml-1). Since the action of plasma catecholamines on the sinus node is potentiated by denervation hypersensitivity, it is suggested that in exercising normal dogs, heart rate control could be ensured by locally released norepinephrine rather than by plasma catecholamines. Plasma catecholamines were assessed in six normal dogs at rest and at various exercise levels (HR = 90-200 beats . min-1) and in blood sampled simultaneously in the aorta and the coronary sinus. Plasma catecholamines in the coronary sinus and aorta were similar at rest (490 +/- 90 vs 580 +/- 80 pg . ml-1, respectively) and at the low-intensity exercise (710 +/- 140 vs 880 +/- 120 pg . ml-1, respectively). For moderate and severe work loads, plasma catecholamine concentrations in the coronary sinus (960 +/- 160 and 1570 +/- 340 pg . ml-1, respectively) were lower than in the aorta (1380 +/- 260 and 2950 +/- 100 pg . ml-1, respectively). These results suggest that in exercising dogs the heart is not a source of plasma catecholamines.

Animals↗
PubMed1999

Catecholamine synthesis is mediated by tyrosinase in the absence of tyrosine hydroxylase.

Catecholamine neurotransmitters are synthesized by hydroxylation of tyrosine to L-dihydroxyphenylalanine (L-Dopa) by tyrosine hydroxylase (TH). The elimination of TH in both pigmented and albino mice described here, like pigmented TH-null mice reported previously (Kobayashi et al., 1995; Zhou et al., 1995), demonstrates the unequivocal requirement for catecholamines during embryonic development. Although the lack of TH is fatal, TH-null embryos can be rescued by administration of catecholamine precursors to pregnant dams. Once born, TH-null pups can survive without further treatment until weaning. Given the relatively rapid half-life of catecholamines, we expected to find none in postnatal TH-null pups. Despite the fact that the TH-null pups lack TH and have not been supplemented with catecholamine precursers, catecholamines are readily detected in our pigmented line of TH-null mice by glyoxylic acid-induced histofluorescence at postnatal day 7 (P7) and P15 and quantitatively at P15 in sympathetically innervated peripheral organs, in sympathetic ganglia, in adrenal glands, and in brains. Between 2 and 22% of wild-type catecholamine concentrations are found in these tissues in mutant pigmented mice. To ascertain the source of the catecholamine, we examined postnatal TH-null albino mice that lack tyrosinase, another enzyme that converts tyrosine to L-Dopa but does so during melanin synthesis. In contrast to the pigmented TH-null mice, catecholamine histofluorescence is undetectable in postnatal albino mutants, and the catecholamine content of TH-null pups lacking tyrosinase is 18% or less than that of TH-null mice with tyrosinase. Thus, these extraordinary circumstances reveal that tyrosinase serves as an alternative pathway to supply catecholamines.

Adrenal Glands↗
PubMed1986

Perturbed pattern of catecholamine-containing neurons in mutant Drosophila deficient in the enzyme dopa decarboxylase.

We have initiated a study of catecholamine-containing neurons in Drosophila melanogaster because of the potential, with this organism, to perturb catecholamine metabolism using genetic tools. The major objectives of this study were (1) to define the pattern of catecholamine-containing neurons and (2) to determine the effect of the absence of dopa decarboxylase (DDC) enzyme activity on the catecholamine-containing neurons. We chose to analyze the catecholamine-containing neurons in the ventral ganglion of the larval CNS. To define the catecholamine-containing neurons, CNSs were dissected and reacted with glyoxylic acid. The catecholamine histofluorescence (CF) neuronal pattern (normal-CF neurons) in the wild-type ventral ganglion is stereotypic. In the mutant ventral ganglia, in the absence of DDC enzyme activity, most normal-CF neurons still exhibit CF, probably indicating the presence of accumulated L-dopa. Interestingly, in the mutant CNSs, additional novel neuronal subsets also exhibit CF. Analysis of CNSs from early developmental stages revealed that the novel-CF neurons become fluorogenic earlier than the normal-CF neurons in the mutant CNS. To determine whether neuronal subsets, in addition to the normal-CF, neurons are able to sequester catecholamines, CNSs from wild-type larvae were incubated in exogenous catecholamine (L-dopa or dopamine). Incubations in L-dopa or dopamine revealed normally nonfluorogenic neurons that are able to take up the amine and become fluorogenic. Among the neurons able to sequester L-dopa or dopamine are subsets that are similar to the novel-CF neurons in the mutant CNS. This similarity is best characterized by a major novel-CF neuronal cluster in the subesophageal-thoracic region. These results suggest that in the absence of DDC activity, subsets of normally nonfluorogenic neurons capable of sequestering L-dopa or dopamine accumulate the fluorogenic catecholamine. Hypotheses that might explain the mode of accumulation of the catecholamine within the novel-CF neurons are considered.

Animals↗
PubMed1984

Redistribution of catecholamines in the ischemic zone of the dog heart.

This study evaluated alterations in catecholamines, blood flow, and indices of tissue damage during early myocardial ischemia in the dog. Of the 27 animals studied, the left anterior descending artery was ligated for 1 hour in 11 and for 3 hours in 13, and 3 underwent sham procedures. The severity of ischemia was determined by the radioactive microsphere and thioflavin S techniques. Myocardial catecholamines were measured radioenzymatically, and catecholamine-containing nerve terminals were visualized histochemically and quantitated with the use of a point-counting method. After both 1- and 3-hour occlusions, there was a greater reduction in catecholamine-containing nerve terminals than in total tissue catecholamines in ischemic tissue. In both ischemic and nonischemic tissue, the relative percentages of total catecholamines as norepinephrine, dopamine, and epinephrine were similar. In the dogs with 3-hour occlusions, values (as a percentage of control values) for total tissue catecholamines were 83% in ischemic subepicardium and 76% in ischemic subendocardium, whereas values for catecholamine-containing nerve terminals were 58% and 51%, respectively. (Only the latter three values were significantly different from control values by analysis of variance). Diffusion of catecholamines from the nerve terminals frequently was noted in the ischemic areas, and degenerative changes in nerve terminals were demonstrated by electron microscopy in 2 animals. These data indicate that catecholamines, primarily as norepinephrine, are released from nerve terminals and accumulate in another tissue compartment in the ischemic myocardium. Quantitative light microscopy showed significant myocyte damage after 1 hour of ischemia in the subendocardium, although not in the subepicardium. There was significant damage in the subepicardium and subendocardium after 3 hours of ischemia. Thus, ischemic injury is associated with the redistribution and abnormal localization of catecholamines in ischemic myocardium, and these phenomena occur during the transmural spread of necrosis in evolving myocardial infarction.

Animals↗
PubMed1976

The correlation between antinociceptive activity of narcotics and their antagonists as measured in the mouse tail-flick test and increased synthesis of brain catecholamines.

The effects of several narcotics, narcotic antagonists-analgesics and narcotic antagonists on the synthesis of dopamine and norepinephrine in mouse brain were estimated and related to their activity in the tail-flick test. Catecholamine synthesis was estimated by measuring the accumulation of 3H-dopamine and 3H-norepinephrine formed from an injection of 3H-tyrosine. Morphine produced dose-related increases in both tail-flick activity and catecholamine synthesis. Each of the narcotic analgesics produced a significant increase in catecholamine synthesis 30 minutes after the subcutaneous injection of an antinociceptive dose (ED80). Under these same conditions, drugs which are inactive in the tail-flick test, such as pentazocine, produced a decrease in catecholamine synthesis and cyclazocine; naloxone and naltrexone were without significant effect. However, cyclazocine, which was inactive in the tail-flick test and did not alter catecholamine synthesis 30 minutes after administration, demonstrated tail-flick activity and produced increased catecholamine synthesis 2 minutes after its administration. Morphine was devoid of either activity 2 minutes after administration. Similarly, at 2 hours after the administration of a dose of morphine (10 mg/kg) that was active in the tail-flick test and increased catecholamine synthesis at 30 minutes, neither tail-flick activity nor increased catecholamine synthesis was observed. Naloxone blocked both the antinociceptive action and the increased catecholamine synthesis produced by both morphine and methadone. The results of these studies indicate that a correlation exists between tail-flick activity of narcotic-like drugs and their ability to increase catecholamine synthesis. These data support the hypothesis that brain catecholamines may be involved in the central mediation of the tail-flick response and other actions of the narcotic analgesics.

Analgesics, Opioid↗
PubMed1995

[Expression of mRNAs coding for catecholamine synthesizing enzymes in human adrenal pheochromocytoma].

Pheochromocytomas synthesize and release catecholamines, which subsequently are related to various clinical manifestations of the disease. However, pheochromocytomas are not innervated and the catecholamine release and synthesis are not initiated by neural impulses. It is still unknown how catecholamine synthesis is regulated in pheochromocytomas. As a first step toward understanding the molecular mechanisms by which catecholamine synthesis is controlled in the tumor, we measured the levels of mRNA coding for the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH) and catecholamines in 6 pheochromocytomas and 2 normal adrenal glands. The TH mRNA level was overexpressed and the catecholamine contents were high in 4 out of 6 pheochromocytomas. There was a close correlation between the TH mRNA level and the catecholamines content in the tumors. We also examined the gene expression of the messengers of other catecholamine synthesizing enzymes, dopamine beta-hydroxylase (DBH) and aromatic 1-amino acid decarboxylase (AADC) in pheochromocytomas. The expression of these genes was in parallel with that of TH mRNA in the tumors. These findings indicate that catecholamine overproduction in pheochromocytomas is mediated by the overexpression of genes coding for catecholamines synthesizing enzymes, TH, DBH, and AADC.

Adrenal Gland Neoplasms↗
PubMed1998

Molecular basis for the stereoselective interactions of catecholamines with alpha-adrenoceptors.

The catecholamines were found to inhibit the binding of the alpha 2-adrenoceptor agonist, [3H]-clonidine, to the recombinant wild type alpha 2a-adrenoceptor (Table 1) with potencies that are consistent with their functional activity in alpha 2-adrenoceptor test systems [6,7]. Mutation of Ser165 to alanine had no significant effect (less than 2-fold) on the affinity of any of the catecholamines for the alpha 2a-adrenoceptor, and in particular, the ratios of affinities between the corresponding (-)- and (+)-enantiomers of the catecholamines were not altered by the point mutation at Ser165. These findings indicate clearly that Ser165, in contrast to predictions made by molecular modeling, plays little if any role in the binding of the catecholamines in general, and cannot be involved in the attachment of the beta-hydroxyl group to the alpha 2a-adrenoceptor. Mutation of either Ser90 on transmembrane helix II or Ser419 on transmembrane helix VII to alanine produced dramatic and selective reductions in the affinity of the (-)-enantiomers of the catecholamines for the alpha 2a-adrenoceptor, with no changes occurring in affinities of the (+)-enantiomers. Thus, the affinities of (-)-norepinephrine and (-)-epinephrine for the Ser90 and Ser419 mutants of the alpha 2a-adrenoceptor were 35-75 fold lower than their affinities for the wild type receptor (Table 1), suggesting that Ser90 and/or Ser419 are involved in the attachment of the beta-hydroxyl groups of the catecholamines to the receptor. Similarly, the affinity of (+/-)-6-fluoronorepinephrine was reduced by 100-fold for the Ser90 mutant receptor (Table 1). Importantly, the affinities of the (+)-enantiomers of the catecholamines, as well as dopamine and epinine, which are the corresponding analogs of norepinephrine and epinephrine which lack the beta-hydroxyl group, were not affected by mutation of Ser90 or Ser419 to alanine (Table 1). Asn293 in transmembrane helix VI has also been proposed to be involved in the interaction of the beta-hydroxyl group of isoproterenol with the beta 2-adrenoceptor [4]. The alpha 2a-adrenoceptor contains three hydroxyl bearing amino acids at a position corresponding to this site (Thr393-Tyr394-Thr395). These amino acids could theoretically form a hydrogen bond with the beta-hydroxyl group of a catecholamine, and therefore could serve as a potential point of attachment. Simultaneous mutation of all three of these amino acids to Ala-Phe-Ala reduced the affinity of the (-)-enantiomers of the catecholamines by 12-20 fold, which is somewhat less than what was observed for mutation of either Ser90 or Ser419 (Table 1). However, in contrast to mutation of Ser90 or Ser419, which had no effect on the affinity of the (+)-enantiomers, mutation of the three residues in transmembrane helix VI did significantly reduce the affinities of the (+)-enantiomers of the catecholamines by approximately 5- to 9-fold, indicating that mutations at these points of the receptor are not selective for the (-)-enantiomers, and are therefore not likely to be involved in the attachment of the beta-hydroxyl group of the catecholamines.

Catecholamines↗
PubMed1999

Cardiovascular control via angiotensin II and circulating catecholamines in the spiny dogfish, Squalus acanthias.

The contributions of circulating angiotensin II (Ang II) and catecholamines to cardiovascular control in the spiny dogfish were investigated by monitoring the effects of exogenous and endogenous dogfish [Asn1, Pro3, Ile5]-Ang II (dfAng II) on plasma catecholamine levels and blood pressure regulation. Bolus intravenous injections of dfAng II (30-1200 pmol kg-1) elicited dose-dependent increases in plasma adrenaline and noradrenaline concentrations, caudal artery pressure (PCA), and systemic vascular resistance (RS), and a decrease in cardiac output (Q). Similar injections of Ang II in dogfish pre-treated with the alpha-adrenoceptor antagonist yohimbine (4 mg kg-1) also elicited dose-dependent increases in plasma catecholamine levels yet the cardiovascular effects were abolished. Dogfish treated with yohimbine were hypotensive and had elevated levels of plasma Ang II and catecholamines. Intravenous injection of the smooth muscle relaxant papaverine (10 mg kg-1) elicited a transient decrease in PCA and RS, and increases in plasma Ang II and catecholamine levels. In dogfish first treated with lisinopril (10(-4) mol kg-1), an angiotensin converting enzyme inhibitor, papaverine treatment caused a more prolonged and greater decrease in PCA and RS, an attenuated increase in plasma catecholamines, and no change in plasma Ang II. By itself, lisinopril treatment had little effect on PCA, and no effect on RS, plasma Ang II or catecholamines. In yohimbine-treated dogfish, papaverine treatment elicited marked decreases in PCA, RS, and Q, and increases in plasma Ang II and catecholamines. Among the three papaverine treatments, there was a positive linear relationship between plasma Ang II and catecholamine concentrations, and the cardiovascular and hormonal changes were most pronounced in the yohimbine + papaverine treatment. Therefore, under resting normotensive conditions, while Ang II does not appear to be involved in cardiovascular control, catecholamines play an important role. However, during a hypotensive stress elicited by vascular smooth muscle relaxation. Ang II indirectly contributes to cardiovascular control by dose-dependently stimulating catecholamine release.

Adrenergic alpha-Antagonists↗
PubMed1982

Catecholamine content of chromaffin granule "ghosts' isolated from bovine adrenal glands.

Studies on the mechanism of catecholamine transport into chromaffin granules is complicated by the release of endogenous catecholamines. To overcome this problem chromaffin granule ghosts have been prepared by many investigators by osmotic lysis of the granules which results in a loss of over 90% of the endogenous catecholamine. However, in the studies reported here, the resulting ghosts still contained 36 +/- 3.9 nmol epinephrine/mg of protein if they were lysed by passage through a Sephadex G-50 column preequilibrated with hypoosmotic media. This residual catecholamine was found to slowly diffuse out of the ghosts in a temperature-dependent process at a rate sufficient to interfere with kinetic analysis of catecholamine transport. Attempts to remove the endogenous catecholamine from the ghosts indicated that most of it could not be removed by further osmotic shock of freeze-thaw treatments, but that over 85% of it was released from the granules by incubating them at 30 degree C for 90 min or by dialysis with a 35 and 86% loss of rate of catecholamine transport into the ghosts, respectively. If the endogenous catecholamine was removed from chromaffin granule ghosts by preincubating them for 90 min at 30 degree C, the resulting ghosts transported catecholamine with a linear Lineweaver-Burk plot indicating a Km of 12 +/- 2 microM. In addition, the resulting ghosts did not leak catecholamines over a 10 min period at 30 degree C, and the transport of catecholamines was blocked by reserpine and enhanced with increasing pH from 6.0 to 8.5.

Adenosine Triphosphate↗
PubMed1998

The tocolytic effect of catecholamines in the gravid rat uterus.

UNLABELLED: Maternal catecholamines increase dramatically in labor because of pain and emotional stress. Because the uterus is richly endowed with both alpha- and beta-adrenergic receptors, catecholamines could alter uterine activity. We assessed the effect of clinically encountered concentrations of these catecholamines on uterine activity and modeled the effect of the abrupt reduction in circulating epinephrine that occurs during effective labor analgesia. Term pregnant rat uteri were excised, and cross-sectional rings were mounted for isometric force recording. Log concentration-response curves for epinephrine, norepinephrine, and their combination on uterine activity were constructed from 10(-12) to 10(-6) M. Catecholamine responses were repeated in the presence of phentolamine, an alpha-adrenergic blocker or propranolol, a beta-adrenergic blocker. The abilities of oxytocin and of washout of catecholamines to reverse catecholamine-induced changes in uterine activity were also assessed. Epinephrine caused dose-dependent reductions in uterine activity, blocked by propranolol. Epinephrine concentrations in the clinical range(10(-9) to 10(-8) M; 100-1000 pg/mL) decreased uterine activity to 49.6% +/- 6.6% (mean +/- SE) of control. Norepinephrine caused a dose-dependent increase in uterine activity, which was blocked by phentolamine. In the clinical range (10(-8) M), uterine activity was 139.2% +/- 13.40% of control. The combination of both catecholamines, however, was nearly as tocolytic as epinephrine alone. Oxytocin antagonized catecholamine-induced tocolysis, and washout of epinephrine or both catecholamines increased uterine activity. We conclude that mixed catecholamines are significantly tocolytic at concentrations encountered in laboring women. In this in vitro model, reduction in epinephrine concentration, comparable to that which occurs during effective analgesia, significantly increases uterine activity. IMPLICATIONS: Maternal catecholamines increase in labor, but epinephrine decreases dramatically after regional analgesia. In this study, we found that norepinephrine and epinephrine together decrease uterine contractile activity and that decreased epinephrine causes significantly increased uterine activity.

Adrenergic alpha-Antagonists↗
PubMed1989

Free and sulfoconjugated catecholamine responses to hypoxia in fetal sheep.

Plasma catecholamines circulate either in conjugated or unconjugated forms. In adult humans, sulfoconjugated catecholamines predominate; however, there is considerable variation between species. In a variety of pathophysiological states catecholamine conjugation is believed to represent an important mechanism of inactivation of high circulating catecholamine levels. To date, there have been few data in developing animals or humans on catecholamine sulfoconjugation. We studied the differences in free and sulfoconjugated catecholamines in full term (141 +/- 1 days) and preterm (123 +/- 1 days) chronically catheterized fetal sheep and determined the changes in free and sulfoconjugated catecholamines in response to hypoxia. The results demonstrate that term and preterm animals have a comparable percentage of basal circulating sulfoconjugated catecholamines (free-to-total ratio 50-60%). In response to hypoxia, both free and sulfoconjugated catecholamines were promptly elevated with significant increases in each by 5 min of hypoxia. This was true for both term and pretern animals. The proportion of free and total catecholamines remained relatively constant during hypoxia despite a 5- to 10-fold increase in circulating levels of each. These data demonstrate that fetal sheep, as early as 80% gestation, have a well developed mechanism for sulfoconjugation and subsequent inactivation of the high circulating levels of catecholamines seen during fetal and newborn life.

Animals↗
PubMed1975

[Peripheral secretion and inactivation of catecholamines (adrenaline, noradrenaline, dopamine)].

In spite of the biochemical relationship between catecholamines (E,NE,DA), the unity of the adrenergic system is only apparent; catecholamines are present in numerous pools, which exhibit different anatomical and cellular localizations, secretory patterns, control of release, physiological functions, inactivation schemes and metabolic behaviour. The main sources of catecholamines in the periphery are the orthosympathetic nervous system, which is permanently active in maintaining homoeostasy, and the adrenal medulla, an essential element in the struggle against stress. In addition to these large pools, catecholamines are found also in extra adrenal chromaffin tissue and in sympathetic ganglions; the latter represents a potential store of amines, whilst ganglionic dopamine-rich interneurones are important links in the regulation of orthosympathetic activity. Rather than by a topographic distinction, it seems more satisfactory to classify the catecholamines spread in adrenergic fields into a small number of pools possessing their own physiological functions and inactivation patterns. Two main pools of catecholamines in the periphery may be described: The functional pool, represented by those catecholamines already released, or able to be released; in this pool are found plasma and adrenal medullary catecholamines and NE from sympathetic nerve endings. The tissue pool, consisting of the synthesis and storage compartments, which are poorly penetrated by plasma pool with respect to their high possibilities for synthesis and storage. Catecholamines from cellular bodies and axons of sympathetic neurons and a part of the adrenal medullary amines may be related to it. Two other pools of catecholamines have to be reported: a potential extrachromaffin pool, which is apparently negligible in the physiological state, but able to exhibit its synthetic and secretory capacities in particularly critical situations; an intraganglionic dopamine pool, which plays a modulator role in ganglionic synaptic transmission; its mode of secretion and inactivation are not necessarily the same as those of the above pools. To such a physiological diversity, specific regulatory processes, correspond the aim of which is, to stop physiological activity of released catecholamines, by means of physical and chemical inactivating mechanisms; to limit the amount of released product by local control of the neuromediator outflow; to minimize losses of active compound by neuronal and cellular uptake and perhaps by sulfoconjugation; to destroy the excess of synthesized or reabsorbed amines when tissue or neuronal concentration becomes too high (tissue metabolism).

Acetylcholine↗
PubMed1985

Does the carrier of chromaffin granules transport the protonated or the uncharged species of catecholamines?

By osmotic lysis in the presence of urea ghosts (60-100 nmol catecholamine/mg prot.) were prepared from chromaffin granules (4-6 mumol catecholamine/mg prot.) of the bovine medulla. In the presence of 1-300 mumol/l 3H-catecholamine and ATP-Mg2+, ghosts show a net uptake of catecholamine. The net uptake is sensitive to reserpine or agents (uncouplers and ammonium) which diminish the electrochemical potential difference for protons at the granule membrane (delta p). The same uptake was found by 3H-counting or by fluorimetric measurements. At various pH-values (pH 6.2-8.2) the Km and Vmax of the ATP-stimulated rate of uptake of 3H-catecholamine into ghosts was determined (at 30 degrees C) to identify the species of catecholamine (protonated, uncharged, or anionic) which is the substrate for the granule carrier. The pH difference (delta pH = pHout - pHin) and the electrical potential difference (delta psi) were determined to calculate delta p under conditions of 3H-catecholamine uptake. When the pHout was increased (pH 6.2, 7.4, 8.2), the apparent Km of uptake decreased (50, 5, 1-2 mumol/l), showing a linear relation between pH and logarithm of Km. The Km was calculated for the uncharged catecholamine (with pK1 = 8.8 and pK2 = 10.0); it was nearly pH-independent and amounted to about 0.2 mumol/l. The Vmax declined only in the extreme pH-range. Between pH 6.6 and 7.8 Vmax and delta p showed a slight increase from 16 to 20 nmoles/(mg prot. X min) and from 110 to 140 mV, resp. In the same pH-range the pHin inside ghosts increased from pH 5.2 to 5.7, whereas delta psi was constant (30 mV). At constant pHout (= 7.3) ammonium (0-30 mmol/l) caused an increase of pHin from 5.5 to 6.6. The increase of pHin was accompanied by an increase of Km from 5 to 20 mumol/l 3H-catecholamine and by a decrease of both Vmax and delta p from 20 to 5 nmoles/(mg prot. X min) and from 123 to 85 mV, respectively. From the dependence of the Km of uptake on pHout is concluded that the uncharged species of catecholamine is transported, whereas the dependence of Km on pHin suggests that the translocation of the catecholamine-carrier complex across the granule membrane is not the rate-limiting step of catecholamine uptake.

Adenosine Triphosphate↗