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 325 records · Page 18Linked to original sources
PubMed1997

Adrenomedullary secretion of DOPA, catecholamines, catechol metabolites, and neuropeptides.

Catecholamines and their metabolites have been proposed as markers of sympathetic nervous system stimulation. However, the adrenal medulla is a rich source of catecholamines and catecholamine metabolites and may play a significant role in plasma levels of these compounds. In addition to adrenal catecholamine metabolite efflux, the role of the catecholamine precursor 3,4-dihydroxyphenylalanine (DOPA) has not been fully evaluated. The simultaneous effluxes of catecholamines, metabolites, DOPA, and neuropeptides were measured in perfusates from isolated dog adrenals. The relative abundance of compounds detected consistently during unstimulated conditions was epinephrine >> norepinephrine > 3,4-dihydroxyphenylglycol > metanephrine > normetanephrine > dopamine > 3,4-dihydroxyphenylacetic acid > 3-methoxy-4-hydroxyphenylglycol > or = DOPA >> [Met]enkephalin >> neuropeptide Y. Effluxes of analytes were not affected by cocaine and the ratios of catecholamines to metabolites increased dramatically with carbachol stimulation, consistent with negligible reuptake into adrenal cells. Thus, most of the 3,4-dihydroxyphenylglycol is expected to be derived from epinephrine and norepinephrine subsequent to translocation from chromaffin vesicles into the cytosol. The efflux of DOPA increased dramatically during stimulation with 30 microM carbachol in a calcium-dependent manner. Efflux of DOPA during the initial stabilization period of the perfusion preparation declined exponentially, in parallel with the effluxes of the catecholamines and neuropeptides but not with metabolites. Evoked release of DOPA was Ca2+-dependent. These data suggest that DOPA can be stored and released exocytotically from chromaffin granules.

Adrenal Medulla↗
PubMed1991

Temporally resolved catecholamine spikes correspond to single vesicle release from individual chromaffin cells.

Secretion of catecholamines from single bovine chromaffin cells in culture was elicited by brief pressure ejections from a micropipette containing nicotine, carbamoylcholine, or potassium ions or by mechanical stimulation. Release was monitored electrochemically with a carbon-fiber microelectrode placed adjacent to the cell. Cyclic voltammetry was used to identify secreted species, whereas constant potential amperometry was used for improved temporal resolution (millisecond range) of catecholamine detection. During secretion, brief current spikes were observed, which were shown to be due to detection of catecholamines by electrooxidation. The spikes have the physical characteristics of multimolecular packets of catecholamines released at random times and locations from the surface of the single cell. The half-width of the spikes was found to increase with an increase in cell-electrode spacing. The properties of the catecholamine spikes correlate well with expectations based on secretion from individual storage vesicles. Spikes do not occur in the absence of Ca2+ in the buffer, and the majority of spikes are found to be distributed between 0.2 and 2 picocoulombs, corresponding to 1-10 attomoles of catecholamine detected. The frequency of the spikes increases with the intensity of the stimulus, but the average quantity of catecholamine in each spike is independent of the stimulus. Thus, these measurements represent time-resolved observation of quantal secretion of catecholamines and provide direct evidence for the exocytotic hypothesis.

Adrenal Medulla↗
PubMed1982

Stimulation of catecholamine secretion from cultured chromaffin cells by an ionophore-mediated rise in intracellular sodium.

The significance of intracellular Na+ concentration in catecholamine secretion of cultured bovine adrenal chromaffin cells was investigated using the monovalent carboxylic ionophore monensin. This ionophore, which is known to mediate a one-for-one exchange of intracellular K+ for extracellular Na+, induces a slow, prolonged release of catecholamines which, at 6 h, amounts of 75-90% of the total catecholamines; carbachol induces a rapid pulse of catecholamine secretion of 25-35%. Although secretory granule numbers appear to be qualitatively reduced after carbachol, multiple carbachol, or Ba2+ stimulation, overall granule distribution remains similar to that in untreated cells. Monensin-stimulated catecholamine release requires extracellular Na+ but not Ca2+ whereas carbachol-stimulated catecholamine release requires extracellular Ca2+ and is partially dependent on extracellular Na+. Despite its high selectivity for monovalent ions, monensin is considerably more effective in promoting catecholamine secretion than the divalent ionophores, A23187 and ionomycin, which mediate a more direct entry of extracellular Ca2+ into the cell. We propose that the monensin-stimulated increase in intracellular Na+ levels causes an increase in the availability of intracellular Ca2+ which, in turn, stimulates exocytosis. This hypothesis is supported by the comparable stimulation of catecholamine release by ouabain which inhibits the outwardly directed Na+ pump and thus permits intracellular Na+ to accumulate. The relative magnitudes of the secretion elicited by monensin, carbachol, and the calcium ionophores, are most consistent with the hypothesis that, under normal physiological conditions, Na+ acts by decreasing the propensity of Ca2+-sequestering sites to bind the Ca2+ that enters the cell as a result of acetylcholine stimulation.

Animals↗
PubMed1981

Changes in catecholamine excretion after short-term tyrosine ingestion in normally fed human subjects.

The effects of ingesting the aromatic amino acid L-tyrosine on excretion of unconjugated catecholamines (dopamine, norepinephrine, and epinephrine) and tyrosine were studied. (Tyrosine is the circulating precursor for the catecholamines, but only a small fraction of the tyrosine in the body is utilized for catecholamine synthesis.) In 10 of 11 normal volunteer subjects, ingestion of 100 mg/kg tyrosine (in three divided doses, preceding each meal, between 8 AM and 5 PM) for 1 day increased the 24-h excretions of total catecholamines by 25%. Only 0.42% of the tyrosine dose was excreted unchanged, but this was sufficient to increase urinary tyrosine by 138%. Both tyrosine and catecholamine excretions varied diurnally; 60% or more of the total output occurred during the day. Since urinary catecholamines reflect molecules synthesized outside the central nervous system, these findings indicate that tyrosine administration can accelerate catecholamine synthesis in the human sympathoadrenal system, probably by enhancing saturation of tyrosine hydroxylase. Therefore, tyrosine may be useful therapeutically in diseases characterized by peripheral catecholamine deficiencies.

Adolescent↗
PubMed1986

Plasma catecholamines in acute magnesium deficiency in weanling rats.

A controlled study was conducted to quantitate plasma catecholamines in magnesium-deficient weanling rats experiencing the seizure-shock episode. Eighty-four male Sprague-Dawley rats each weighing 35.6 +/- 0.3 g (mean +/- SEM) were fed purified diets to which was added 150 mg magnesium/100 g (Mg-150) or no magnesium (Mg-0). Studies were conducted between d 5 and 8. Plasma and bone magnesium and calcium were measured by atomic absorption spectrophotometry, and plasma catecholamines by radioenzymatic assay using 3H. Compared with Mg-150 rats, the Mg-0 rats showed reduced weight gain (P less than 0.001); reduced plasma magnesium (P less than 0.001) and reduced bone magnesium (P less than 0.001) with no corresponding changes in calcium concentration; and a 25% mortality by d 8. Pair-feeding and 80-dB noise provoked no changes in plasma catecholamines in Mg-150 rats, but both strychnine-induced seizures in Mg-150 rats and seizures induced by 80-dB noise in Mg-0 rats were accompanied by massive increases in plasma catecholamines. In contrast, 80-dB noise in Mg-0 provoked a massive increase in plasma catecholamines (P less than 0.001). However, gross pulmonary pathology developed only in Mg-0-shocked rats, not Mg-150-shocked animals. The study provides no evidence for a role of catecholamines in the pathogenesis of Mg-0 shock. The weanling rat displayed the ability to release massive quantities of three catecholamines during the final stages of acute magnesium deficiency and to normalize the plasma catecholamine levels within 16 h after seizure shock.

Animals↗
PubMed1985

Mechanism of the effect of droperidol to induce catecholamine efflux from the adrenal medulla.

The study was undertaken to determine whether droperidol had an effect to induce catecholamine efflux from the adrenal medulla as a mechanism for the possible pressor effect of droperidol in patients with pheochromocytoma and, if so, to ascertain the site of action of this compound. The efflux of catecholamines from perfused dog adrenals was increased from control level, 0.15 micrograms/min, to 0.66 micrograms/min by the administration of droperidol 6.6 microM. This effect of droperidol was not dependent on extracellular Ca++, in contrast to acetylcholine. The concomitant secretion of catecholamines and dopamine-beta-hydroxylase was observed in response to acetylcholine and caffeine. However, droperidol-, histamine-, and reserpine-induced catecholamine efflux was not accompanied by dopamine-beta-hydroxylase release. In additional studies, chromaffin granules were isolated with a Millipore filter technique from the bovine adrenal medulla and were incubated for 10 min in an isotonic medium to examine the direct effects of droperidol. Droperidol did not enhance the efflux of catecholamines from the granules in contrast to histamine. The uptake of 14C-norepinephrine into the granules was inhibited by droperidol in a manner comparable to reserpine. The results suggest that droperidol induces catecholamine efflux from adrenal medullary cells and the efflux probably is caused by a nonexocytotic mechanism. A contributing mechanism was an inhibition of catecholamine uptake into chromaffin granules, resulting in an increased diffusion of catecholamines out of the cell.

Acetylcholine↗
PubMed1993

Determinants of catecholamine and cortisol responses to lower extremity revascularization. The PIRAT Study Group.

BACKGROUND: Surgical trauma elicits diffuse changes in hormonal secretion and autonomic nervous system activity. Despite studies demonstrating modulation of the stress response by different anesthetic/analgesic regimens, little is known regarding the determinants of catecholamine and cortisol responses to surgery. METHODS: Plasma catecholamines and cortisol secretion data were obtained from 60 patients undergoing lower extremity revascularization. Patients were randomized to receive either general anesthesia combined with patient-controlled intravenous morphine (GA) or epidural anesthesia combined with epidural fentanyl analgesia (RA). All aspects of intra- and postoperative clinical care were defined by written protocol. Plasma catecholamines were measured before induction, intraoperatively, and for the first 18 h postoperatively (by HPLC). Urine cortisol was measured intra- and postoperatively using RIA. Data were evaluated using univariate and multivariate analyses to evaluate demographic and perioperative variables as determinants of stress hormone secretion. RESULTS: Plasma catecholamines increased during skin closure in the GA group, and remained higher relative to the RA group in the postoperative period. Multivariate analysis indicated that age and anesthetic regimen predicted increases in catecholamines during skin closure (P < 0.005), although duration of surgery, blood loss, and body temperature were not correlated. Early postoperative norepinephrine concentrations were correlated with pain score and duration of surgery (P < 0.004), but not with anesthetic management, blood loss, or body temperature. All postoperative norepinephrine levels were highly correlated (r = 0.7) with norepinephrine levels during skin closure. Cortisol excretion was higher postoperatively than intraoperatively. No patient or perioperative variable predicted cortisol excretion, and cortisol excretion was not correlated with catecholamine levels at any time. CONCLUSIONS: These data indicate that patient factors, such as age and inherent sympathetic responsivity, are important determinants of the catecholamine response to surgery. Modulation of the norepinephrine response by regional anesthesia/analgesia appears to be related, in part, to superior analgesia. The lack of correlation between catecholamine and cortisol secretion indicates that the stress response may consist of discrete systems responding to different stimuli.

Adult↗
PubMed2002

Growth stimulation of intestinal commensal Escherichia coli by catecholamines: a possible contributory factor in trauma-induced sepsis.

Trauma is well recognized to result in the immediate and sustained release of stress-related neurochemicals such as the catecholamine norepinephrine. Past work has shown that in addition to their ability to function as neurotransmitters, catecholamines can also directly stimulate the growth of a number of pathogenic bacteria. The development of trauma-associated sepsis has often been linked to the ability of otherwise normal commensal bacteria to invade and penetrate the gut mucosal barrier. Therefore, the aim of our study was to examine whether catecholamines could also stimulate the growth of commensal Escherichia coli strains of the type present in the intestinal tract at the time of a traumatic event. Herein we report that the growth of a range of non-pathogenic isolates of E. coli of human and environmental origin was significantly increased in the presence of catecholamines. A primary mechanism by which catecholamines increase bacterial growth was shown to be iron removal from lactoferrin and transferrin and subsequent acquisition by bacteria. The 3,4-dihydroxybenzoyl (catechol) structure of the catecholamines was further demonstrated to be critical to iron acquisition. The synthetic catecholamine inotropes dobutamine and isoprenaline, as well as norepinephrine metabolites that retained the catechol structure were also active, whereas norepinephrine metabolites in which the catechol moiety had been modified were not. A role for catecholamine-mediated bacterial iron supply in the pathophysiology of gut-derived sepsis due to trauma is proposed.

Catecholamines↗
PubMed1997

Hypoxia-induced catecholamine secretion in isolated newborn rat adrenal chromaffin cells is mimicked by inhibition of mitochondrial respiration.

1. In newborn mammals, systemic hypoxia provokes catecholamine secretion from the adrenal medulla. In contrast to adults, this release is independent of sympathetic innervation. We have studied the cellular processes involved in hypoxia-induced catecholamine secretion, employing fluorimetric techniques to measure changes in [Ca2+]i, NADH and mitochondrial potential, and voltammetric techniques to record changes in PO2 and catecholamine secretion. 2. In adrenal chromaffin cells freshly dissociated from newborn rats, severe hypoxia increased [Ca2+]i and secretion of catecholamines, indicating that the response of the newborn adrenal medulla to hypoxia is an intrinsic property of these cells. Discrete quantal secretory events were identifiable, suggesting an exocytotic mechanism of secretion. 3. Hypoxia-induced secretion was only seen when PO2 fell below 5 mmHg, similar to the threshold arterial PO2 reported to stimulate release in vivo. Such oxygen tensions also inhibited mitochondrial metabolism, shown by an increase in NADH autofluorescence. We therefore explored the involvement of mitochondria in oxygen sensing. Inhibition of mitochondrial respiration either by CN- at complex IV or by rotenone at complex I mimicked severe hypoxia, reversibly increasing both [Ca2+]i and catecholamine secretion. The CN(-)-induced depolarization of the mitochondrial inner membrane potential preceded the increase in [Ca2+]i by approximately 6 s. 4. The effects of severe hypoxia and CN- on [Ca2+]i and catecholamine secretion were not additive, suggesting a common mechanism. 5. Chemical anoxia failed to increase [Ca2+]i in a significant proportion of cells dissociated from 2- to 4-week-old rats. Thus, the sensitivity to hypoxia is specific to adrenal chromaffin cells dissociated from newborn rats. 6. These data indicate that hypoxia-induced catecholamine secretion in the newborn adrenal medulla is mediated by reversible inhibition of mitochondrial respiration, leading to an increase in [Ca2+]i and catecholamine secretion.

Adrenal Glands↗
PubMed1980

Exocytotic release of catecholamine from perfused adrenal gland of guinea-pig induced by veratridine.

1 Experiments were carried out on perfused adrenal glands of guinea-pig to determine whether veratridine caused the exocytotic release of catecholamine by comparing its effect with that of splanchnic nerve stimulation and secretagogues such as acetylcholine and excess K+. 2 Veratridine (100 microM) and excess K+ (56 mM) caused secretion of catecholamine and dopamine-beta-hydroxylase (DBH) activity in the venous effluents in the presence of atropine (30 microM) and hexamethonium (2 mM). Splanchnic nerve stimulation in the presence or absence of physostigmine (100 nM) and infusion of acetylcholine in the presence of physostigmine had the same effect. In all the responses, the release of DBH tended to last for a longer period than that of catecholamine. 3 The ratio of catecholamine to DBH activity appearing in the venous effluents was approximately 9, regardless of the method of stimulation. This value was close to the ratio of catecholamines to the 'soluble' DBH activity found in the chromaffin granules. 4 All the types of stimulation used caused a proportional release of adenine nucleotides and catecholamines in the effluents. The adenine nucleotides were mainly adenosine 5'-phosphate. 5 The ratio of catecholamine to adenine nucleotides was approximately 11, regardless of the method of stimulation. 6 It is suggested that the release of catecholamine induced by veratridine occurs by exocytosis in adrenal glands of guinea-pig.

Acetylcholine↗
PubMed1986

Effects of Bay K 8644 on cat adrenal catecholamine secretory responses to A23187 or ouabain.

Calcium ionophore A23187 increases the rate of spontaneous catecholamine release from cat adrenal glands perfused at 37 degrees C with oxygenated Krebs bicarbonate solution, in a time- and Ca-concentration-dependent manner. The secretory profile obtained with the ionophore was not modified in the presence of the Ca channel activator Bay K 8644. Ouabain also enhanced the rate of spontaneous catecholamine outputs in a time- and concentration-dependent manner. The threshold ouabain concentration capable of producing a clear, yet delayed secretory response was 10(-6) M. Increasing ouabain concentrations up to 10(-4) M enhanced catecholamine release and shortened the time to peak release. The dihydropyridine Ca channel activator Bay K 8644 (10(-6) M) markedly potentiated the secretory effects of all ouabain concentrations used (10(-7)-10(-4) M). However, the most impressive potentiations were seen at 10(-5)M ouabain; while at this concentration ouabain alone released 2.6 +/- 0.07 micrograms catecholamines per 30 min, in the presence of Bay K 8644 the release was 73.4 +/- 5.7 micrograms per 30 min. Conversely, at a fixed ouabain concentration (10(-5) M), the potentiation was also dependent on the Bay K 8644 concentration (10(-8)-10(-5) M). Although K deprivation inhibits Na pumping as does ouabain, Bay K 8644 did not modify the rate of catecholamine release evoked by K removal from the perfusion medium. Potassium deletion, nimodipine or high Mg all reversed the fully developed secretory response evoked by ouabain plus Bay K 8644. In glands depolarized by continuous perfusion with high K solutions, once the secretory response was inactivated, the introduction of ouabain caused an enhancement of the catecholamine secretory rate. This increase was dependent on the extracellular Na concentration and was not affected by Bay K 8644. In the presence of 6 mm Na the secretory effects of Bay K 8644 plus ouabain were abolished. 7 These results are compatible with the following conclusions: (i) Bay K 8644 potentiates only those catecholamine secretory responses that are known to be mediated through the activation of voltagesensitive Ca channels; the drug does not seem to affect secretory responses by acting on the membrane Na/Ca exchange system or at some intracellular Ca-dependent component of the secretory machinery of Ca buffering systems. (ii) It is likely that ouabain enhances the rates of adrenal catecholamine release by a dual mechanism: chromaffin cell depolarization and activation of a membrane Na/Ca exchange system.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1972

Relaxing effects of catecholamines on mammalian heart.

1. The effect of catecholamines on the time course and amplitude of contraction and on KCl-induced contractures has been studied in mammalian hearts.2. Marked and reproducible contractures could be obtained in mammalian ventricular trabeculae and papillary muscles after beta-adrenergic block with propanolol or if the hearts were depleted of their catecholamine stores by reserpine or by chemical denervation with 6-hydroxydopamine.3. In neonatal hearts with lower endogenous catecholamine stores and poorly developed sarcoplasmic reticulum KCl contractures are easily produced.4. Catecholamines potentiate twitch tension and relax the contracture tension under all of the above circumstances.5. The relaxant effect of catecholamines is present during the time course of a twitch. This increased relaxation rate as well as the shortening of the time-to-peak of tension is independent of the variation in the duration of the action potential.6. The shortened relaxation time is present when the action potential is shortened with anodal repolarization or prolonged with cathodal depolarization (voltage-clamp).7. The relaxant effect of catecholamines on the twitch is temperature and rate dependent. The effect is observed in the presence of high or low concentrations of calcium.8. The presence of catecholamines is necessary for full relaxation of mammalian heart muscle under high performance conditions or states of calcium overload.9. It is proposed that catecholamines exert their relaxant effect independent of their positive inotropic effect by stimulating the sequestering system (sarcoplasmic reticulum, mitochondria or sarcolemma) for calcium.

Action Potentials↗
PubMed1985

A dopaminergic receptor modulates catecholamine release from the cat adrenal gland.

Nicotine evokes the release of catecholamines from perfused cat adrenal glands in a concentration-dependent manner, the median effective concentration for nicotine being 5 microM. Two 2 min pulses of 5 microM-nicotine, 40 min apart (S1 and S2) gave net catecholamine outputs of 7.64 and 3.55 micrograms/8 min, respectively. The ratio S2/S1 in control glands was 0.5. Increasing concentrations of apomorphine (1-10 microM) markedly inhibited catecholamine release during the second nicotine pulse (S2). At 1 microM-apomorphine, the release during S2 was significantly reduced to 16% of S1; with 10 microM-apomorphine, the secretory response was reduced further to only 3% of S1, the ratio S2/S1 being 0.03. The presence of haloperidol, sulpiride or picobenzide (each 0.5 microM) during S2, completely reversed the inhibition of catecholamine release produced by apomorphine. Haloperidol itself increased the nicotinic secretory response during S2; so, while the ratio S2/S1 was 0.5 in control conditions, this ratio increased significantly to 0.95 if haloperidol (0.5 microM) was present during S2, suggesting that the presence of this dopaminergic antagonist removed a negative feed-back mechanism that inhibits nicotine-evoked catecholamine release. If present during S2, dopamine (1 microM) also markedly inhibited catecholamine release evoked by nicotine; this inhibition was again reversed by 0.5 microM-haloperidol. Neither the opiate antagonist naloxone nor the alpha-adrenoceptor blocking agent phentolamine (at concentrations of 0.5-5 microM) affected the inhibition by apomorphine of the secretory response to nicotine. These data strongly suggest that the cat adrenal medulla chromaffin cell membrane contains a dopaminergic receptor which modulates the catecholamine secretory process triggered by stimulation of the nicotinic cholinoceptor. The fact that dopamine is released in measurable amounts, together with adrenaline and noradrenaline, from perfused cat adrenal glands in response to nicotinic stimulation (V. Ceña, unpublished results), favours a role for this dopaminergic receptor in modulating catecholamine release from the chromaffin cell.

Adrenal Glands↗
PubMed1991

O-Methylated and sulfoconjugated catecholamines: differential activities at human platelet alpha 2-adrenoceptors.

The physiological effects of the sulfoconjugates of epinephrine, norepinephrine, and the 3-O-methylated catecholamines, metanephrine, normetanephrine, and methoxytyramine were examined with regard to their alpha 2-adrenoceptor binding properties and aggregation activity in human platelets. Sulfoconjugation of catecholamines resulted in the loss of both their competitive potency for [3H]yohimbine binding and their influence on platelet aggregation. O-Methyl substituted catecholamines showed attenuation of their alpha 2-adrenoceptor binding affinities when compared with those of the corresponding non-esterified amines. Unlike the free amine epinephrine, which stimulated platelet aggregation, the O-methylated catecholamine derivatives inhibited aggregation. Inhibition was dose-dependent and restricted to the alpha 2-adrenoceptor mediated aggregation response stimulated by epinephrine (1 microM) or potentiated by subthreshold concentrations of epinephrine (30-300 nM) in the presence of subaggregatory doses of vasopressin (10-30 nM). Collagen- and ADP-induced platelet aggregation was not affected. The hydrophilic beta-antagonist CGP 12177 displayed no effects. However, high concentrations (0.1 mM) of both isomers of the strongly lipophilic beta-adrenoceptor antagonist propranolol inhibited the actions of all aggregators by stabilizing the membrane. Such a nonspecific membrane interaction of the methylated catecholamines could be excluded because of their low lipid solubility calculated in a n-octanol-phosphate buffer system at pH 7.4. We suggest therefore that methylated catecholamines are biological alpha 2-adrenoceptor antagonists acting on alpha 2-adrenoceptor stimulated reactions of human platelets. Whether this receptor antagonism is relevant to other human tissues needs clarification. Sulfated catecholamines, however, are wholly ineffective at this receptor site and may constitute a pathway to control the concentration of the active free catecholamines.

Adrenergic beta-Antagonists↗
PubMed1995

Inhibition by BMS 186295, a selective nonpeptide AT1 antagonist, of adrenal catecholamine release induced by angiotensin II in the dog in vivo.

The aim of the present study was to investigate whether a novel nonpeptide AT1 selective antagonist, BMS 186295 (BMS), can antagonize adrenal catecholamine release induced by local administration of angiotensin II (AII) in anesthetized dogs. Plasma catecholamine concentrations in adrenal venous and aortic blood were determined by an HPLC-electrochemical method. AII was locally administered to the left adrenal gland in the absence and presence of BMS. In the first group (n = 7), local infusion (0.5 mL/min, 1 min) of AII (0.001-1.0 micrograms/mL) resulted in a significant dose-dependent increase in the basal secretion of adrenal catecholamines. Aortic catecholamine levels and mean aortic pressure remained unchanged at all doses tested. In the second group (control, n = 10), four repeated infusions (at intervals of 15 min) of AII at 0.1 micrograms/mL resulted in significant increases of adrenal catecholamine secretion compared with the baseline. In the third group receiving BMS given locally to the gland (n = 8), the basal adrenal catecholamine secretion was not significantly altered by BMS itself at any dose tested. However, the net catecholamine response to AII (0.1 micrograms/mL) was significantly and dose dependently attenuated by approximately 40, 60, and 80% in the presence of BMS at doses of 0.1, 1.0, and 10 micrograms/mL, respectively, compared with the control group. The study indicates that BMS dose dependently blocks AII-induced catecholamine secretion in the dog adrenal gland in vivo.

Adrenal Glands↗
PubMed2003

Catecholamines act via a beta-adrenergic receptor to maintain fetal heart rate and survival.

Mice lacking catecholamines die before birth, some with cardiovascular abnormalities. To investigate the role of catecholamines in development, embryonic day 12.5 (E12.5) fetuses were cultured and heart rate monitored. Under optimal oxygenation, wild-type and catecholamine-deficient fetuses had the same initial heart rate (200-220 beats/min), which decreased by 15% in wild-type fetuses during 50 min of culture. During the same culture period, catecholamine-deficient fetuses dropped their heart rate by 35%. Hypoxia reduced heart rate of wild-type fetuses by 35-40% in culture and by 20% in utero, assessed by echocardiography. However, catecholamine-deficient fetuses exhibited greater hypoxia-induced bradycardia, reducing their heart rate by 70-75% in culture. Isoproterenol, a beta-adrenergic receptor (beta-AR) agonist, reversed this extreme bradycardia, restoring the rate of catecholamine-deficient fetuses to that of nonmutant siblings. Moreover, isoproterenol rescued 100% of catecholamine-deficient pups to birth in a dose-dependent, stereo-specific manner when administered in the dam's drinking water. An alpha-AR agonist was without effect. When wild-type fetuses were cultured with adrenoreceptor antagonists to create pharmacological nulls, blockade of alpha-ARs with 10 microM phentolamine or beta-ARs with 10 microM bupranolol alone or in combination did not reduce heart rate under optimal oxygenation. However, when combined with hypoxia, beta-AR blockade reduced heart rate by 35%. In contrast, the muscarinic blocker atropine and the alpha-AR antagonist phentolamine had no effect. These data suggest that beta-ARs mediate survival in vivo and regulate heart rate in culture. We hypothesize that norepinephrine, acting through beta-ARs, maintains fetal heart rate during periods of transient hypoxia that occur throughout gestation, and that catecholamine-deficient fetuses die because they cannot withstand hypoxia-induced bradycardia.

Adrenergic beta-Antagonists↗
PubMed1997

Ser165 of transmembrane helix IV is not involved in the interaction of catecholamines with the alpha-2a-adrenoceptor.

Molecular modeling studies have predicted that the beta-hydroxyl group of the catecholamines interacts with the beta 2-adrenoceptor at the serine residue at position 165 (Ser165) located on transmembrane helix IV; however, this has not been confirmed by site-directed mutagenesis. It has been inferred that this site, which is conserved in all of the nine known alpha- and beta-adrenoceptor subtypes, is also involved in the interaction of catecholamines with the alpha 2a-adrenoceptor. To test the hypothesis that the beta-hydroxyl group of the catecholamines interacts with Ser165 of the alpha 2a-adrenoceptor, we prepared a mutant alpha 2a-adrenoceptor where Ser165 was mutated to alanine. Mutation of Ser165 of the alpha 2a-adrenoceptor to alanine had no effect on the affinity of dopamine (which lacks the beta-hydroxyl group) or either enantiomer of norepinephrine or epinephrine (both of which possess the beta-hydroxyl group), indicating that Ser165 is not involved in the interaction of the catecholamines with the alpha 2a-adrenoceptor. We have previously shown that mutation of Ser90, located in transmembrane helix II, to either alanine or cysteine produces a selective reduction in the affinity of the (-)-enantiomers of the catecholamines for the alpha 2a-adrenoceptor, with no effect on the (+)-enantiomers or the corresponding beta-desoxy analogs. This is consistent with the known stereoselectivity involved in the interactions of catecholamines with the alpha 2a-adrenoceptor. The results of the present investigation indicate that Ser165 is not involved in the interaction of catecholamines with the alpha 2a-adrenoceptor. Because all known alpha-adrenoceptor subtypes have a serine residue at a position corresponding to Ser90 of the alpha 2a-adrenoceptor, it would appear that this site represents an important point for attachment of the beta-hydroxyl group of catecholamines.

Alanine↗
PubMed2005

Dehydroepiandrosterone sulfate and allopregnanolone directly stimulate catecholamine production via induction of tyrosine hydroxylase and secretion by affecting actin polymerization.

Adrenal cortical cells of zona reticularis produce the neuroactive steroids dehydroepiandrosterone (DHEA), its sulfate ester dehydroepiandrosterone sulfate (DHEAS), and allopregnanolone (ALLO). An interaction between zona reticularis and adrenal medulla has been postulated based on their close proximity and their interwoven borders. The aim of this paper was to examine in vitro the possible paracrine effects of these steroids on catecholamine production from adrenomedullary chromaffin cells, using an established in vitro model of chromaffin cells, the PC12 rat pheochromocytoma cell line. We have found the following: 1) DHEA, DHEAS, and ALLO increased acutely (peak effect between 10-30 min) and dose-dependently (EC50 in the nanomolar range) catecholamine levels (norepinephrine and dopamine). 2) It appears that the acute effect of these steroids involved actin depolymerization/actin filament disassembly, a fast-response cellular system regulating trafficking of catecholamine vesicles. Specifically, 10(-6) m phallacidin, an actin filament stabilizer, completely prevented steroid-induced catecholamine secretion. 3) DHEAS and ALLO, but not DHEA, also affected catecholamine synthesis. Indeed, DHEAS and ALLO increased catecholamine levels at 24 h, an effect blocked by L-2-methyl-3-(-4-hydroxyphenyl)alanine and 3-(hydrazinomethyl)phenol hydrochloride, inhibitors of tyrosine hydroxylase and L-aromatic amino acid decarboxylase, respectively, suggesting that this effect involved catecholamine synthesis. The latter hypothesis was confirmed by finding that DHEAS and ALLO increased both the mRNA and protein levels of tyrosine hydroxylase. In conclusion, our findings suggest that neuroactive steroids exert a direct tonic effect on adrenal catecholamine synthesis and secretion. These data associate the adrenomedullary malfunction observed in old age and neuroactive steroids.

Actins↗