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 235 records · Page 13Linked to original sources

Atlas of catecholamine perikarya, varicosities and pathways in the brainstem of the cat.

By application of a modified glyoxylic acid--paraformaldehyde histofluorescence technique, catecholamine perikarya, varicosities, and pathways were delineated within the brainstem of kittens that were either untreated, pretreated pharmacologically, or injected intracerebrally with 6-OHDA. Three principle catecholamine cell groups were identified within the medulla and pons; the dorsomedial medullary cell group, the dorsolateral pontine cell group, and a ventrolateral cell group extending from the medulla into the pons. Induced axonal accumulation of catecholamines with intracerebral 6-OHDA injections revealed a major longitudinal catecholamine bundle which courses in a dorsolateral position through the entire brainstem tegmentum. The dorsomedial medullary and dorsolateral pontine cell groups contribute ascending and descending fibers to this bundle. Axons of the ventrolateral pontomedullary cells also feed into the bundle at successive levels through radially coursing transverse fibers. Via this major dorsolateral conduit and its ventrally and medially coursing tributaries, catecholamine fibers and terminals are distributed to multiple nuclei through the brainstem. The regions of the catecholamine cell groups and the serotonin raphe nuclei all receive a dense catecholamine innervation. Varicosities are also dense in the visceral cranial nerve nuclei, moderately dense in most somatic spinal and cranial nerve motor nuclei, and moderate to light in sensory cranial nerve and relay nuclei. The lateral and ventromedial reticular formation are moderately innervated by varicose catecholamine fibers that traverse these regions. The longitudinal catecholamine bundle continues caudally into the lateral funiculus to descend into and innervate the spinal cord. Rostrally it continues into the tegmental fascicles of the midbrain to ascend into and innervate the diencephalon and there join the medial forebrain bundle to ascend into the telencephalon. Thus, the catecholamine neurons utilize this dorsolateral longitudinal bundle to distribute collaterals to multiple bulbar nuclei and to travel beyond the brainstem to innervate the spinal cord and forebrain.

Animals↗

Catecholamine mechanisms in medio-basal hypothalamus influence prolactin but not growth hormone secretion.

Medio-basal hypothalamic (MBH) catecholamine mechanisms in the regulation of prolactin and growth hormone (GH) secretion were investigated in unanesthetized rats with chronic indwelling venous cannulae and bilateral MBH directed intracerebral guide cannulae. MBH injections of the catecholamine-specific neurotoxin 6-hydroxydopamine (6-OHDA; 2 micrograms base in 0.5 microliter 0.9% saline) had no effect upon basal prolactin or GH secretion. Examination of catecholamine fluorescence indicated that MBH 6-OHDA treatment produced widespread disruption of MBH catecholamine afferents but did not destroy tuberoinfundibular dopamine neurons of the arcuate nucleus, nor median eminence catecholamine structures. MBH injections (0.5 microliter, 0.032 M solutions) of dopamine, noradrenaline or adrenaline all produced statistically significant increases in plasma prolactin levels. The potency of these 3 catecholamines in evoking prolactin release differed markedly, adrenaline having the greatest effect. MBH catecholamine injections had no effect upon plasma GH levels compared to saline injected controls. The present data suggest that MBH catecholamine afferents are unimportant in the regulation of basal patterns of GH or prolactin secretion. As MBH catecholamine injections stimulate prolactin release this region may contain a prolactin-facilitatory catecholamine mechanism which is capable of generating prolactin surges in response to certain environmental or endogenous stimuli.

Animals↗

The effects of catecholamines on ventilation in rainbow trout during hypoxia or hypercapnia.

This study assessed the effects of experimentally elevated plasma catecholamine levels on gill ventilation in rainbow trout (Oncorhyncus mykiss) exposed to various external ventilatory stimulants. Trout were exposed to hypoxia (water PO2 (PwO2) = 90 Torr) or hypercapnia (water PCO2 (PwCO2) = 4.5 Torr) for 30 min. These conditions caused gill ventilation volume (Vw) to increase by 2.3- and 1.5-fold, respectively, but did not stimulate release of catecholamines into the blood. While the stimulus (hypoxia or hypercapnia) was maintained, fish were given a bolus injection (0.3 ml), followed by intra-arterial infusion (0.6 ml.h-1), of a catecholamine mixture (2 x 10(-5) mol.l-1 adrenaline + 5 x 10(-6) mol.l-1 noradrenaline) to mimic the physiological concentrations and ratios of these catecholamines observed under more severe hypoxic or hypercapnic conditions. In hypoxic fish, this treatment caused a significant, but transient (5 min) depression of ventilation while during hypercapnia, the administration of exogenous catecholamines caused a more prolonged hypoventilatory response. These hypoventilatory responses occurred despite a catecholamine-induced blood acidosis (a potential ventilatory stimulant). To assess the importance of initial Vw and/or blood respiratory status on catecholamine-mediated hypoventilation, these experiments were repeated under hyperoxic (PwO2 = 640 Torr) hyperoxic hypercapnic (PwO2 = 510 Torr, PwCO2 = 4.8 Torr) or normoxic (PwO2 = 151 Torr) conditions in which Vw was either depressed (3.9-fold during hyperoxia) or unaffected. Intra-arterial infusion of catecholamines did not affect Vw under either of these experimental conditions. These results demonstrate that during a respiratory challenge, such as hypoxia or hypercapnia, physiologically relevant levels of circulating catecholamines can depress Vw and therefore do not support a stimulatory role for circulating catecholamines in the control of ventilation in fish.

Animals↗

Muscarinic transmission decreases the number of SIF cells demonstrating catecholamine histofluorescence in rat superior cervical ganglia.

Preganglionic electrical stimulation of the cervical sympathetic trunk to the rat superior cervical ganglia produced a mean reduction in the number of visible small intensely fluorescent (SIF) cells demonstrating catecholamine histofluorescence to 32% of the unstimulated contralateral control. The reduction in the number of catecholamine-positive SIF cells required the presence of specific blockers of catecholamine uptake and synthesis and was dependent on normal synaptic transmission. No change in the number of catecholamine-positive SIF cells was observed when ganglionic transmission occurred in solutions containing both hexamethonium and atropine or with atropine alone (97% of the unstimulated control). Furthermore, preganglionic stimulation in the presence of high magnesium/low calcium solutions, which effectively blocked synaptic transmission, prevented the stimulation-induced decrease in the number of catecholamine-positive SIF cells. Prolonged antidromic stimulation of the internal carotid nerve only reduced the number of catecholamine-positive SIF cells to 75% of the unstimulated contralateral control. These results suggest that preganglionic synaptic impulses can induce the release of catecholamines from SIF cells via muscarinic receptor activation. Furthermore, the necessity for pharmacological intervention of uptake and synthesis blockers of catecholamines in order to detect the synaptically-induced reduction in the number of catecholamine-positive SIF cells, suggests that synaptic transmission also modulates the synthesis of catecholamines in SIF cells within the rat superior cervical ganglia.

Action Potentials↗

Influx of 22Na through acetylcholine receptor-associated Na channels: relationship between 22Na influx, 45Ca influx and secretion of catecholamines in cultured bovine adrenal medulla cells.

The effects of carbachol, veratridine and high K on the influx of 22Na were investigated in relation to the influx of 45Ca and the secretion of catecholamines in cultured bovine adrenal medulla cells, in which stimulation of nicotinic but not muscarinic acetylcholine receptor causes the secretory response. (1) Carbachol caused a rapid influx of 22Na, influx of 45Ca and secretion of catecholamines, all of which occurred within 1 min and leveled off thereafter. Influx of 45Ca and secretion of catecholamines caused by carbachol were not inhibited by tetrodotoxin, but were greatly reduced in Na-free medium. Nicotine evoked an influx of 22Na and it was antagonized by hexamethonium and d-tubocurarine but not by tetrodotoxin. Muscarine had no effect on 22Na influx. The concentration-response curve of carbachol for 22Na influx was quite similar to that for 45Ca influx. (2) Veratridine induced a sustained influx of 22Na, influx of 45Ca and secretion of catecholamines, all of which were antagonized by tetrodotoxin. Influx of 45Ca and secretion of catecholamines due to veratridine were not observed in Na-free medium. (3) High K caused an influx of 45Ca and secretion of catecholamines but did not cause an influx of 22Na. High K-induced influx of 45Ca and secretion of catecholamines were not inhibited by tetrodotoxin nor by Na removal. (4) Magnesium, an inhibitor of voltage-dependent Ca channels, inhibited the influx of 45Ca and secretion of catecholamines caused by carbachol, veratridine and high K. These results indicate that cultured bovine adrenal medulla cells have at least three distinct ion channels: (1) nicotinic acetylcholine receptor-associated Na channels which are not inhibited by tetrodotoxin, (2) voltage-dependent Na channels which are kept activated by veratridine and inhibited by tetrodotoxin and (3) voltage-dependent Ca channels. Influx of Ca through voltage-dependent Ca channels is the common ionic event for the secretion of catecholamines caused by either carbachol, veratridine or high K. It seems that the influx of Na through acetylcholine receptor-associated Na channels as well as voltage-dependent Na channels, activates voltage-dependent Ca channels which triggers the secretion of catecholamines.

Adrenal Medulla↗

Contribution of catechol O-methyltransferase to the removal of accumulated interstitial catecholamines evoked by myocardial ischemia.

Catechol O-methyltransferase (COMT) plays an important role for clearance of high catecholamine levels. Although myocardial ischemia evokes similar excessive catecholamine accumulation, it is uncertain whether COMT activity is involved in the removal of accumulated catecholamines evoked by myocardial ischemia. We examined how COMT activity affects myocardial catecholamine levels during myocardial ischemia and reperfusion. We implanted a dialysis probe into the left ventricular myocardial free wall and measured dialysate catecholamines levels in anesthetized rabbits. Dialysate catecholamine levels served as an index of myocardial interstitial catecholamine levels. We introduced myocardial ischemia by 60 min occlusion of the main coronary artery. The ischemia-induced dialysate catecholamines levels were compared with and without the pretreatment with entacapone (COMT inhibitor, 10 mg/kg, i.p.). Acute myocardial ischemia progressively increased dialysate catecholamine levels. Acute myocardial ischemia increased dialysate norepinephrine (NE) levels (20,453+/-7186 pg/ml), epinephrine (EPI) levels (1724+/-706 pg/ml), and dopamine (DA) levels (1807+/-800 pg/ml) at the last 15 min of coronary occlusion. Inhibition of COMT activity by entacapone augmented the ischemia-induced NE levels (54,306+/-6618 pg/ml), EPI levels (2681+/-567 pg/ml), and DA (3551+/-710 pg/ml) levels at the last 15 min of coronary occlusion. Myocardial ischemia evoked NE, EPI, and DA accumulation in the myocardial interstitial space. The inhibition of COMT activity augmented these increments in NE, EPI, and DA. These data suggest that cardiac COMT activity influences on the removal of accumulated catecholamine during myocardial ischemia.

Animals↗

Catecholamines and their metabolites.

The research on biosynthesis, physiology, pharmacology, regulation and degradation of catecholamines has continuously increased for more than 50 years. This is not unexpected because of the fact that catecholamines are involved in so many life processes such as nerve conduction, blood circulation and hormone regulations in health and disease. This demands that methods for their determination should be improved, and in fact during the years a number of analytical methods have been published. About 20 years ago radioenzyme techniques with thin-layer chromatographic (TLC) separation of radiolabelled catecholamine derivatives were developed which greatly contributed to our knowledge of physiological concentrations of catecholamines in biological media, particularly in plasma and brain. Radioimmune methods were successful for analysis of a number of analytes, but for catecholamines radioimmunoassays developed slowly. We believe that the greatest potential for radioimmunochemical methods lies in their ability to localize catecholamines and metabolites at the cellular and subcellular levels. With the advent of gas chromatographic-mass spectrometric (GC-MS) and high-performance liquid chromatographic (HPLC) procedures analysis of catecholamines improved greatly., The equipment for GC-MS is expensive and requires technical skillfulness, but in experienced hands a lot of new biological data have emerged. An outstanding quality with GC-MS is that the method offers the ability to identify unknown compounds and is relatively free from interferences from extraneous compounds. In comparison with GC-MS, HPLC is versatile and has gained a widespread use. Applications for research in the catecholamine field are numerous. In general, the sensitivity and specificity are satisfactory with HPLC, but it should be borne in mind that a number of pitfalls can obscure the results. This involves both sample handling, clean-up and chromatographic procedures. At present, HPLC is the most expanding field in chromatographic determination of catecholamines and their metabolites. This is particularly the case for HPLC with electrochemical detection which has revolutionized our analytical potential in this field. These chromatographic procedures continue to develop. The prerequisites for further improved methods such as capillary zone electrophoresis and combined HPLC-MS are at hand and hopefully will soon come into more general use for analysis of catecholamines in biological samples.

Animals↗

The enteric parasite Entamoeba uses an autocrine catecholamine system during differentiation into the infectious cyst stage.

Enteric amoebae of the genus Entamoeba travel from host to host in an encysted form. We previously showed that in vitro cyst development of Entamoeba invadens requires the addition of defined amounts of multivalent galactose-terminated molecules, such as mucin, to the cultures. The amoeba surface lectin that binds mucin is presumed to convey transmembrane signals when clustered by the ligand, but the signaling molecules that function downstream of the lectin are not known. We report here that Entamoeba encystation was induced in the absence of galactose ligand when catecholamines were added to the encystation medium. Micromolar amounts of both epinephrine and norepinephrine induced encystation. Of a variety of synthetic catecholamine agonists tested, only beta(1)-adrenergic receptor agonists supported encystation, whereas alpha- and beta(2)-adrenergic receptor agonists did not. Only beta(1)-adrenergic receptor antagonists inhibited encystation, and did so even when exogenous catecholamines were not added, indicating that catecholamine binding is required for encystation and suggesting an endogenous source of the ligand. High performance liquid chromatography analysis of Entamoeba extracts showed that the amoebae themselves contain catecholamines and at least one of these is released when the cells are stimulated to encyst with galactose-terminated ligands. The presence of catecholamine binding sites on the surface of amoeba trophozoites was confirmed using radiolabeled catecholamine antagonist. Amoeba encystment was inhibited by addition of beta(1)-adrenergic receptor antagonist to cells that were stimulated to differentiate with either galactose ligand or catecholamines, but not with dibutyryl cAMP. This suggests that the amoeba catecholamine receptor functions downstream of the galactose lectin and upstream of adenylyl cyclase. This enteric protozoan parasite, therefore, contains the components of an autocrine catecholamine ligand-receptor system that may act in conjunction with a galactose lectin to regulate differentiation into the infectious cyst stage.

Animals↗

Effect of catecholamines on Na/H exchange in vascular smooth muscle cells.

Catecholamines were found to activate Na/H exchange in a concentration-dependent manner in primary cultures of vascular smooth muscle cells (VSMC). The potency order was found to be epinephrine greater than norepinephrine greater than isoproterenol. The major pathway for catecholamine effects appeared to be via interaction with an alpha 1 adrenergic receptor. In addition, it was found that alpha 1 receptor-mediated Na/H exchange in VSMC was increased by angiotensin II and inhibited by 12-O-tetradecanoyl phorbol-13-acetate (TPA). Adrenergic receptors have been shown to be coupled to both adenylate cyclase and to inositol phosphate release (Leeb-Lundberg, L. M. F., S. Cotecchia, J. W. Lomasney, J. F. DeBernadis, R. J. Lefkowitz, and M. G. Caron, 1985, Proc. Natl. Acad. Sci. USA, 82:5651-5655.). It was found that catecholamines increased AMP levels in the potency order isoproterenol greater than norepinephrine greater than epinephrine and the receptor involved was a beta adrenergic receptor. Since these findings did not parallel the results obtained for catecholamine stimulation of Na/H exchange, an increase in AMP levels was probably not the mechanism by which major pathway for catecholamine-stimulated Na/H exchange in VSMC (via the alpha 1 receptor) was activated. When the effects of catecholamines were measured on inositol phosphate release, the potency order for catecholamine stimulation was epinephrine greater than norepinephrine greater than isoproterenol, and the receptor involved was an alpha 1 adrenergic receptor. In addition, angiotensin II increased and TPA inhibited catecholamine-stimulated inositol phosphate release. Since these findings paralleled the results obtained for catecholamine stimulation of Na/H exchange, inositol phosphate release may be the mechanism by which the major pathway for catecholamine-stimulated Na/H exchange in VSMC (via the alpha 1 receptor) was activated.

Amiloride↗

Voltage-independent catecholamine release mediated by the activation of muscarinic receptors in guinea-pig adrenal glands.

1. The differences between the mechanisms of muscarinic and nicotinic receptor-mediated catecholamine secretion with respect to their dependence on voltage changes and extracellular Ca were examined using perfused adrenal glands of the guinea-pig. 2. Acetylcholine (ACh, 10(-6) to 10(-3) M) caused a dose-dependent increase in catecholamine secretion. The ED50 value for ACh was 7 x 10(-5) M. In the presence of atropine (10(-5) M), the dose-response curve for ACh was shifted to the right. Hexamethonium (5 x 10(-4) M) preferentially reduced the responses to higher concentrations of ACh (greater than 10(-5) M). Pilocarpine (5 x 10(-4) M) and nicotine (3 x 10(-5) M) also stimulated catecholamine release. 3. During perfusion with isotonic KCl solution, ACh and pilocarpine, but not nicotine, evoked catecholamine secretion. These responses were abolished by atropine (10(-6) M). Pilocarpine-stimulated catecholamine secretion was enhanced during perfusion with isotonic KCl solution. Under these conditions, hexamethonium (10(-3) M) significantly augmented ACh-evoked catecholamine release. 4. During perfusion with either Ca-free isotonic KCl or Ca-free Locke solution, ACh and pilocarpine caused a partial increase in catecholamine secretion whereas nicotine and high K solution (56 mM) did not. The responses to ACh and pilocarpine were completely inhibited by atropine but not by hexamethonium. 5. When guinea-pig adrenal glands were perfused with isotonic KCl solution containing 2.2 mM Ca which was subsequently removed and replaced with EGTA, ACh-induced catecholamine secretion was similar in magnitude to that observed during perfusion with Locke solution. 6. We conclude that both nicotinic and muscarinic receptors are involved in ACh-induced catecholamine secretion from guinea-pig adrenal chromaffin cells. Activation of muscarinic or nicotinic receptors appears to stimulate catecholamine release through different mechanisms with respect to both voltage-dependence and Ca requirements.

Acetylcholine↗

Pentazocine-induced catecholamine efflux from the dog perfused adrenals.

This study has been undertaken to determine whether pentazocine induces catecholamine efflux from the adrenal medulla as a mechanism for its sympathomimetic effect. Dog isolated adrenals were perfused retrogradely with modified Locke's solution. The efflux of catecholamines from dog perfused adrenals was increased from the resting output of 0.18 +/- 0.04 micrograms min-1 (mean +/- s.e.), to 0.47 +/- 0.13 micrograms min-1 by the administration of pentazocine (50 microM). The pentazocine-induced catecholamine efflux was dose-dependent in the 50-400 microM dose range. This effect of pentazocine was not inhibited by either a combination of atropine and (+)-tubocurarine, or verapamil, in contrast to acetylcholine-induced catecholamine release. There was no significant difference in potency among stereoisomers, i.e. (+)-, (-)- and (+/-)-pentazocine, in inducing catecholamine efflux. Naloxone did not influence the effects of either (+)- or (-)-pentazocine. The interaction of pentazocine with acetylcholine-induced catecholamine release was also examined. Both (+)- and (-)-pentazocine inhibited acetylcholine-induced catecholamine release dose-dependently, and these inhibitory effects were not reversed by naloxone. Acetylcholine-induced catecholamine release was accompanied by increased dopamine-beta-hydroxylase release, whereas pentazocine-induced catecholamine efflux was not. These results suggest that pentazocine directly acts on the adrenal medulla to induce catecholamine efflux via a non-exocytotic mechanism, and that opioid receptors do not play a role in this action.

Acetylcholine↗

The effect of sodium and calcium ions on the release of catecholamines from the adrenal medulla: sodium deprivation induces release by exocytosis in the absence of extracellular calcium.

1. Perfusing bovine adrenal glands with Na(+)-free Locke solution for 15-40 min did not modify the increase in the release of catecholamines from glands stimulated by acetylcholine. However, after 80-100 min of perfusion with Na(+)-free solution, the response to acetylcholine stimulation was decreased or abolished.2. Immediately after switching the perfusion medium to Na(+)-free solution, there was a sharp increase (6-10 times over control values) in catecholamine output.3. Graded substitution of Na(+) in the perfusion fluid enhanced the output of catecholamines. This increase in the output of amines was linearly related to the logarithm of the extracellular Na(+) concentration.4. The release of catecholamines in the absence of Na(+) was not reduced by the presence of atropine and hexamethonium nor by the omission of Ca(2+) in the presence of EDTA or EGTA.5. Excess of Mg(2+) in the perfusion fluid reduced (10 mM-Mg(2+)) or blocked (20 mM-Mg(2+)) the increase in the output of catecholamines induced by Na(+) deprivation in the presence or absence of extracellular Ca(2+).6. Na(+) deprivation induced release of catecholamines during perfusion of the glands with depolarizing concentrations (56 mM) of K(+).7. In the presence or the absence of extracellular Ca(2+), the increase in the output of catecholamines induced by Na(+) deprivation was accompanied by an increase in the output of dopamine beta-hydroxylase, but not of lactate dehydrogenase. In addition, during perfusion with Ca(2+) free solution, Na(+) deprivation induced a parallel increase in both catecholamine and adenosine triphosphate outputs.8. The ratios of catecholamines to dopamine beta-hydroxylase and catecholamines to adenosine triphosphate determined in the perfusates collected from glands during perfusion with Na(+)-free medium were similar to those measured in the soluble contents of isolated chromaffin granules. These results provided biochemical evidence in favour of exocytosis as the mechanism of secretion during Na(+) deprivation.

Acetates↗

Is the platelet phenolsulfotransferase involved in the sulfoconjugation of plasma catecholamines?

Catecholamines are predominantly present in the sulfoconjugated forms in human plasma. Phenolsulfotransferase (EC 2.8.2.1), which catalyses the sulfation of phenolic compounds, is widely distributed in human tissues. In blood, a phenolsulfotransferase, more specific for catecholamine sulfation is found exclusively in platelets. Free and sulfoconjugated catecholamines were measured in plasma and platelets of healthy volunteers and compared with those present in patients with uremia or pheochromocytoma to determine the ability of platelet phenolsulfotransferase to sulfurylate plasma catecholamines. In patients with pheochromocytoma, the rise in free and sulfoconjugated plasma catecholamines is accompanied by a simultaneous rise of these molecules in platelets. In uremia, where the level of plasma catecholamines is normal, the rise in the sulfoconjugates is not accompanied by a concomitant increase in either free or sulfoconjugated catecholamines in platelets. Platelet phenolsulfotransferase activity remains unchanged in pheochromocytoma and uremia. These data indicate that the platelet phenolsulfotransferase is involved in the sulfation of the catecholamines present in platelets, but its contribution, if any, to the high level of sulfoconjugated catecholamines found in plasma is negligible. This assertion is confirmed by our observations in thrombocytopenic patients. Indeed, despite the very low number of platelets and the absence of plasma phenolsulfotransferase activity, thrombocytopenic patients have normal plasma levels of free and sulfoconjugated catecholamines.

Adrenal Gland Neoplasms↗

In vivo demonstration of a paracrine, inhibitory action of Met-enkephalin on adrenomedullary catecholamine release in the rat.

The present study was an attempt to assess the inhibitory effect of methionine-enkephalin (Met-Enk) on adrenal catecholamine release under in vivo conditions employing a microdialysis system. One adrenal gland of intact male rats was implanted with a microdialysis system. One day after surgery, the adrenal dialysis system was connected to a perfusion pump and Ringer solution or a Ringer solution containing Met-Enk, naloxone (Nal), or a combination of Met-Enk and Nal was used for dialysis; dialysate fractions were collected at 5-min intervals. Catecholamine secretion was stimulated by an iv injection of 1.4 mumol (200 micrograms) acetylcholine (Ach). Met-Enk-immunoreactive material in adrenal medulla extracts and dialysate fractions was analyzed by reverse phase HPLC combined with Met-Enk RIA. Under resting conditions, adrenal release rates of norepinephrine and epinephrine into the Ringer solution were constant. After Ach application secretion of both catecholamines increased about 2.7-fold. Within 10 min after the injection, catecholamine levels returned to baseline levels. Intra-adrenal application of Met-Enk reduced Ach-stimulated epinephrine, but not norepinephrine, secretion significantly; application of Nal did not affect Ach-stimulated catecholamine secretion in the initial fraction after Ach injection, but significantly prolonged amine secretion after the cholinergic stimulus. Application of Nal followed by a combined application of Met-Enk and Nal was without an effect on the amount of catecholamines released in the initial fraction after Ach injection compared to that in the control group. Thus, naloxone prevented the inhibitory effect of Met-Enk on Ach-stimulated CA release. HPLC analysis of adrenal medulla extracts followed by Met-Enk RIA revealed that several forms of Met-Enk are present in chromaffin cells, whereas in adrenal dialysates only one, albeit broad, signal of Met-Enk immunoreactivity was detectable. We demonstrate in vivo a paracrine or autocrine action of Met-Enk on Ach-stimulated catecholamine release by applying the peptide directly into the adrenal gland via a microdialysis system. We conclude that neuropeptides endogenous to the adrenal gland not only reduce the amplitude of catecholamine secretion in response to an Ach stimulus but, in addition, modulate the duration of catecholamine secretion. This is demonstrated by a prolonged catecholamine secretion if opiate receptors are blocked by Nal.

Adrenal Medulla↗

Activation of angiotensin II subtype 2 receptor induces catecholamine release in an extracellular Ca(2+)-dependent manner through a decrease of cyclic guanosine 3',5'-monophosphate production in cultured porcine adrenal medullary chromaffin Cells.

We have previously demonstrated that CGP 42112 (AT(2) agonist > or =1 nM) markedly reduces catecholamine biosynthesis through AT(2), which is the major angiotensin II (AngII) receptor subtype in cultured porcine chromaffin cells. Also, we have shown that CGP 42112 (> or =1 nM) induces a reduction in cGMP production in these cells. The present study showed that AngII reduced cGMP production via AT(2) in a manner similar to that found with CGP 42112. AngII (1 nM) significantly increased catecholamine secretion from cultured porcine adrenal medullary chromaffin cells. The stimulation was significantly inhibited by PD 123319 (AT(2) antagonist). The stimulation was moderately, but significantly, attenuated by CV-11974 (AT(1) antagonist, > or =10 nM), suggesting an involvement of AT(1). Moreover, CGP 42112 (> or =10 nM) markedly increased catecholamine release from these cells. The stimulation by CGP 42112 was abolished by PD 123319, whereas CV-11974 had no effect, indicating that this response is also mediated by AT(2). We further examined whether extracellular Ca(2+) is involved in the stimulatory effect of AT(2) on catecholamine secretion. Removal of external Ca(2+) significantly suppressed either AngII plus CV-11974 (100 nM; which simulates specific AT(2) stimulation) or CGP 42112- induced catecholamine secretion. AngII plus CV-11974 or CGP 42112 caused a sustained increase in intracellular Ca(2+) ([Ca(2+)](i)), as determined in fura-2-loaded chromaffin cells in an extracellular Ca(2+)-dependent manner. In the presence of EGTA, the subsequent addition of AngII with CV-11974 and CGP 42112 did not cause any increase in [Ca(2+)](i) levels. Consistent with this finding, CGP 42112 (10 nM to 1 microM) did not alter inositol triphosphate (IP(3)) production, a messenger for mobilization of Ca(2+) from intracellular storage sites. In addition, the intracellular Ca(2+) chelator 1,2-bis(2-amino-phenoxy)ethane-N,N,N',N'- tetraacetic acid acetoxymethylester (BAPTA) did not affect CGP 42112-induced catecholamine release. We tested whether a decrease in cGMP was the cause of the stimulatory effect of AT(2) on catecholamine secretion. Pretreatment with 8-bromo-cGMP (1 mM) prevented the stimulatory effect of AngII plus CV-11974 and CGP 42112 on both catecholamine secretion and [Ca(2+)](i). When 8-bromo-cGMP was added after application of AngII plus CV-11974 or CGP 42112, [Ca(2+)](i) induced by these agents was gradually reduced toward the baseline values. Similarly, guanylin completely abolished the AngII- plus CV-11974-induced increase in both NE secretion and [Ca(2+)](i). The Ca(2+) channel blockers, nicardipine and omega-conotoxin G VIA, at 1 microM in both cases, were also effective in inhibiting AT(2) stimulation-induced secretion. On the other hand, neither T-type voltage-dependent Ca(2+) channel blockers, flunarizine, nor Ni(2+) affected catecholamine release caused by AT(2) stimulation. These findings demonstrate that AT(2) stimulation induces catecholamine secretion by mobilizing Ca(2+) through voltage-dependent Ca(2+) channels without affecting intracellular pools and that these effects could be mediated by a decrease in cGMP production.

Adrenal Medulla↗

Nitric oxide and the control of catecholamine secretion in rainbow trout Oncorhynchus mykiss.

An in situ saline-perfused posterior cardinal vein preparation was used to assess the role of nitric oxide (NO) in the regulation of basal and stimulus-evoked catecholamine secretion from rainbow trout Oncorhynchus mykiss chromaffin cells. Addition of the NO donor, sodium nitroprusside (SNP) to the inflowing perfusate abolished catecholamine secretion during electrical field stimulation, thereby establishing the potential for NO to act as a potent inhibitor of catecholamine release. A possible role for endogenously produced NO was established by demonstrating that stimulus-evoked (depolarizing levels of KCl or electrical field stimulation) catecholamine secretion was markedly stimulated in the presence of the nitric oxide synthase (NOS) inhibitors l-NAME and 7-NI. Although in vitro experiments demonstrated that catecholamine degradation was enhanced by NO in a dose-dependent manner, the dominant factor contributing to the reduction in catecholamine appearance in the perfusate was specific inhibition of catecholamine secretion. Subsequent experiments were performed to identify the NOS isoform(s) contributing to the inhibition of stimulus-evoked catecholamine secretion. Inducible NOS (iNOS; an enzyme that can be activated in the absence of Ca2+), although present in the vicinity of the chromaffin cells (based on mRNA measurements), does not appear to play a role because stimulus-evoked NO production was eliminated during perfusion with Ca2+-free saline. The potential involvement of endothelial NOS (eNOS) was revealed by showing that hypoxic perfusate evoked NO production and corresponded with an inhibition of stimulus-evoked catecholamine secretion; chemical removal of the endothelium (using saponin) prevented the production of NO during hypoxia. However, because removal of the endothelium did not affect NO production during electrical field stimulation, it would appear that the neuronal form of NOS (nNOS) is the key isoform modulating catecholamine secretion from trout chromaffin cells.

Analysis of Variance↗

Catecholamines are required for the acquisition of secretory responsiveness by sweat glands.

The sympathetic innervation of sweat glands undergoes a developmental change in transmitter phenotype from catecholaminergic to cholinergic. Acetylcholine elicits sweating and is necessary for development and maintenance of secretory responsiveness, the ability of glands to produce sweat after nerve stimulation or agonist administration. To determine whether catecholamines play a role in the development or function of this system, we examined the onset of secretory responsiveness in two transgenic mouse lines, one albino and the other pigmented, that lack tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Although both lines lack TH, their catecholamine levels differ because tyrosinase in pigmented mice serves as an alternative source for catecholamine synthesis (Rios et al., 1999). At postnatal day 21 (P21), 28 glands on average are active in interdigital hind footpads of albino TH wild-type mice. In contrast, fewer than one gland is active in albino TH null mice, which lack catecholamines in gland innervation. Treatment of albino TH null mice with DOPA, a catecholamine precursor, from P11 to P21 increases the number of active glands to 14. Pigmented TH null mice, which have faint catecholamine fluorescence in the developing gland innervation, possess 12 active glands at P21, indicating that catecholamines made via tyrosinase, albeit reduced from wild-type levels, support development of responsiveness. Gland formation and the appearance of cholinergic markers occur normally in albino TH null mice, suggesting that catecholamines act directly on gland cells to trigger their final differentiation and to induce responsiveness. Thus, catecholamines, like acetylcholine, are essential for the development of secretory responsiveness.

Acetylcholine↗

In vivo catecholamine extraction during continuous hemodiafiltration in inotrope-dependent patients.

Many critically ill patients require inotropic or vasopressor support to maintain adequate oxygen delivery. Removal of catecholamines by continuous hemodiafiltration (CHD) could alter exogenous catecholamine requirements. The authors have studied hemodynamic state, catecholamine clearances, and catecholamine requirements in 12 critically ill patients (mean APACHE II score, 24.5) receiving CHD. Hemodynamic parameters were assessed before CHD initiation, and at 4 and 24 hours of therapy. Simultaneous determinations of serum and ultradiafiltrate dopamine (D), norepinephrine (NE), and epinephrine (E) concentrations were obtained. There were no significant changes in any of many hemodynamic parameters measured during CHD. Mean catecholamine requirements were not altered by CHD. Plasma catecholamine levels were not significantly affected by CHD (mean values at 0, 4, and 24 hours: D: 10,801, 12,056, and 8,797 pg/ml; NE: 1124, 566, and 926 pg/ml; E: 1,420, 1,383, and 843 pg/ml). Catecholamine clearances from CHD (D:43.7 ml/min; NE: 43.5 ml/min; and E: 46.6 ml/min) resulted in daily excretion of only 379 micrograms D, 32.9 micrograms NE, and 37.2 micrograms E. Clearances of catecholamines by CHD represented a daily loss of less than 0.1% of the administered load. In conclusion, although CHD can remove circulating catecholamines, cumulative daily catecholamine extraction is minimal in pharmacologic terms, and has no impact on hemodynamic status.

Acute Kidney Injury↗