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PubMed1983

Phospholipase A2 inhibitors block catecholamine secretion and calcium uptake in cultured bovine adrenal medullary cells.

Phospholipase A2 is a calcium-dependent enzyme which produces membrane fusogens. The possibility that it may be involved in exocytosis of catecholamine from primary dissociated cultures of bovine adrenal medullary cells was investigated by studying the effects on catecholamine secretion and 44Ca2+ uptake of three phospholipase A2 inhibitors: p-bromophenacyl bromide (BPB), Upjohn Compound 1002, and mepacrine. The three compounds completely inhibited catecholamine secretion induced by the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP), elevated K+, and Ba2+. The inhibition of nicotinic agonist-induced secretion by mepacrine may have been caused by direct nicotinic antagonist activity of the drug. The phospholipase inhibitors also inhibited 45Ca2+ uptake into the cells stimulated by DMPP and elevated K+. Inhibition of 45Ca2+ uptake and catecholamine secretion exhibited identical dose-response curves. Other effects of the inhibitors were also investigated. Compound 1002 had no effect on 45Ca2+ efflux from the cells in the presence of either normal or reduced Na+ concentrations. BPB inhibited DMPP-stimulated phosphorylation of tyrosine hydroxylase which, like exocytosis, is dependent on a rise in cytosolic Ca2+. The data suggest that phospholipase A2 inhibitors block catecholamine secretion from intact chromaffin cells by blocking Ca2+ influx.

Acetophenones↗
PubMed1982

Elevation of urinary catecholamines and their metabolites following tyrosine administration in humans.

A single oral dose of tyrosine (100 or 150 mg/kg) caused significant increases in urinary levels of norepinephrine (NE), epinephrine (E), dopamine (DA), 3-methoxy-4-hydroxyphenylglycol (MHPG), vanilmandelic acid (VMA), and homovanillic acid (HVA) during the first 2 hr after its ingestion; water administration failed to produce such changes. The temporal patterns of these increases paralleled those of previously described increases in plasma tyrosine. Since urinary catecholamines derive from peripheral sources, while the catecholamine metabolites in urine may reflect both CNS and peripheral catecholamine turnover, these findings indicate that tyrosine administration may accelerate catecholamine synthesis in and release from cells throughout the human body. Tyrosine may thus constitute a useful agent for treating central or peripheral disorders associated with insufficient release of catecholamines.

Adolescent↗
PubMed1981

Plasma catecholamine levels in the diagnosis and management of pheochromocytoma.

Plasma catecholamine levels have been determined before, during and after operation in seven consecutive patients operated upon for pheochromocytoma. The method used permits the simultaneous determination of norepinephrine, epinephrine and dopamine. All patients had increased levels of one or several catecholamines while hypertensive. Two of seven patients had normal levels of catecholamines while they were normotensive. Spontaneous or provoked attacks strongly increased plasma catecholamine levels. The present method may prove to be of value as a simple method to ascertain or exclude pheochromocytoma. During operation plasma norepinephrine and epinephrine levels increased up to 600fold when the tumor was manipulated. The unpredictable rapid and large variations in levels of catecholamines found during operation suggest preoperative alpha-adrenergic receptor blockade and monitoring of central circulation.

Adolescent↗
PubMed1995

Catecholamines in human dental pulp. A combined immunohistochemical and chromatographic study.

Pharmacological studies have suggested that nerve-released catecholamines may play an important role in the regulation of vascular tone and in the modulation of sensory nerve activity in animal teeth. We have used tyrosine hydroxylase-immunohistochemistry to detect catecholamine-producing cells in human dental pulp and high performance liquid chromatography to identify and quantitate catecholamines in this tissue. Tyrosine hydroxylase-immunoreactivity was confined to a sub-population of nerve fibres that were mainly localized around blood vessels. Considerable concentrations of norepinephrine (17.8 +/- 3.75 pg/mg tissue) and much lower concentrations of dopamine and epinephrine (0.27 +/- 0.10 and 0.19 +/- 0.11 pg/mg, respectively) were measured in all samples examined. It is suggested that catecholamines in human dental pulp are exclusively contained in nervous structures that are mainly associated with blood vessels and that norepinephrine is the candidate neurotransmitter of these nerve fibres. These data provide the basis to further studies addressed to clarify the possible functions of catecholamines in human dental pulp during physiological as well as inflammatory situations.

Adolescent↗
PubMed1995

Endogenous catecholamines are not necessary for ischaemic preconditioning in the isolated perfused rat heart.

OBJECTIVE: The mechanism of the protective effect of ischaemic preconditioning in the myocardium is not yet known. The aim of this study was to test the hypothesis that endogenous myocardial catecholamines may be mediators of preconditioning. METHODS: To test whether endogenous catecholamines are involved in preconditioning, experiments were performed in hearts from rats which had been catecholamine depleted with either reserpine or 6-hydroxydopamine. Experiments were also done to determine if noradrenaline can mimic preconditioning. RESULTS: Catecholamine depletion with either reserpine or 6-hydroxydopamine had no effect on preischaemic coronary flow or cardiac function. Ischaemic preconditioning (four episodes of 5 min global ischaemia and 5 min reperfusion) resulted in a significant increase in postischaemic cardiac function and a 50% decrease in lactate dehydrogenase (LDH) release following 30 min ischaemia and 30 min reperfusion compared with non-preconditioned hearts. Reserpine pretreatment did not affect the response to ischaemia or to preconditioning, although LDH release tended to be greater than in normal hearts, especially in the non-preconditioned group. Although 6-hydroxydopamine significantly increased postischaemic cardiac function in the preconditioned group, no other index of ischaemic damage (for example, LDH release, left ventricular end diastolic pressure) was affected. Further studies showed that 10 nmol.min-1 noradrenaline did not affect the severity of ischaemia, indicating that it does not mimic preconditioning. CONCLUSIONS: Endogenous catecholamines are not necessary for ischaemic preconditioning in isolated rat hearts and play little or no role in the functional responses to ischaemia.

Animals↗
PubMed1995

Effects of catecholamines on the residual sodium channel dependent slow conduction in guinea pig ventricular muscles under normoxia and hypoxia.

OBJECTIVE: The aim was to study the effects of catecholamines (isoprenaline and noradrenaline) on the action potential upstroke and conduction velocity in guinea pig ventricular papillary muscles. METHODS: The upstroke velocity and the conduction velocity of the action potential were recorded by conventional two-microelectrode techniques in the guinea pig ventricular papillary muscle superfused with normoxic and hypoxic Tyrode solution of various potassium concentrations ([K+]o 2.7-16.7 mM), stimulated at 0.2 Hz. RESULTS: Under normoxic conditions, the upstroke of action potentials is composed of two components, dV/dtmax,fast followed by dV/dtmax,slow, when the muscle were perfused with relatively high [K+]o (10.8-16.7 mM). The dV/dtmax,fast is a measure of the residual (mostly inactivated) sodium current, while the dV/dtmax,slow is a measure of calcium current. The conduction velocity at 13-17 mM [K+]o ranged from 30-40 cm.s-1 (slow conduction) with depolarised membrane potentials of about -60 mV. Isoprenaline in increasing concentrations (0.01-1 microM) did not significantly alter the conduction velocity but altered the ionic channels responsible for the slow conduction from residual sodium channel to calcium channel. In the presence of D600 (2 microM) or 1-verapamil (2.2 microM), isoprenaline (0.1 microM) rapidly decreased dV/dtmax,fast without increasing dV/dtmax,slow and a conduction block occurred. In the presence of pindolol (2 microM), all the effects of isoprenaline on dV/dtmax,fast, dV/dtmax,slow, and conduction velocity were abolished. Noradrenaline has the same effects as isoprenaline, although the potency was much less. Under hypoxic conditions, the effects of catecholamines on the dV/dtmax,fast was the same as under normoxic conditions. CONCLUSIONS: Catecholamines alter the ionic channel responsible for the slow conduction of reentry circuit from residual sodium to calcium channel, or vice versa, depending on the local concentrations of catecholamines. In the presence of a calcium antagonist, catecholamines strongly depress the (dV/dtmax,fast dependent) slow conduction, leading to a complete block of conduction, under both normoxia and hypoxia.

Action Potentials↗
PubMed1994

C-type natriuretic peptide stimulates catecholamine synthesis through the accumulation of cyclic GMP in cultured bovine adrenal medullary cells.

We examined the effects of C-type natriuretic peptide (CNP) on cyclic GMP production and catecholamine synthesis in cultured bovine adrenal medullary cells. 1) CNP increased intracellular cyclic GMP content in a concentration-dependent manner (10-1000 nM). 2) The cyclic GMP production induced by 1 microM CNP reached a 200-fold increase, and the effect of CNP was most potent among the natriuretic peptide family. 3) The CNP-induced cyclic GMP production was attenuated by endothelin (1 microM) and angiotensin II (0.1-1 microM). 4) When the cells were cultured with hypertonic NaCl medium, the CNP-induced cyclic GMP production was potentiated in a time (1-4 days)- and concentration (25-100 mM)-dependent manner. 5) CNP stimulated the synthesis of 14C-labeled catecholamines from [14C] tyrosine but not from [14C] dopa. The stimulatory effect of CNP on the 14C-labeled catecholamine synthesis was observed at the concentrations of 100 to 100 nM. 6) 8-Bromo cyclic GMP, a membrane-permeable cyclic GMP analog, and sodium nitroprusside, an activator of soluble guanylate cyclase, also stimulated the synthesis of 14C-labeled catecholamines from [14C]tyrosine, whereas C-ANF, a specific ligand for the ANP-C (clearance) receptor that does not increase cyclic GMP content, failed to stimulate the synthesis of 14C-labeled catecholamines. 7) CNP (1 microM) as well as 8-bromo cyclic GMP and sodium nitroprusside increased the activity of tyrosine hydroxylase in the cells. These results suggest that in the adrenal medulla, CNP is a potent agonist for cyclic GMP production, which is modulated by endothelin, angiotensin II and the hypertonic NaCl condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMedDate not supplied

The role of catecholamines, age, and fitness on blood pressure reactivity to dynamic exercise in patients with essential hypertension.

OBJECTIVE: To determine the relationship between exercise blood pressure (BP) and catecholamine levels in hypertensive subjects and, secondarily, to evaluate the influence of age and fitness level. DESIGN: Descriptive correlational. SETTING: Midwestern, university-affiliated medical center. SUBJECTS: 27 hypertensive subjects, mean age 45 years, who were free of antihypertensive medications. OUTCOME MEASURES: BP and plasma catecholamines (norepinephrine and epinephrine). INTERVENTION: Subjects were given an incremental maximal exercise test on a cycle ergometer beginning at 25 watts with workloads increasing by 25 watts every 2 minutes until exhaustion. Plasma catecholamines were measured at rest, at 100 watts, and at maximal exercise. BP, heart rate, and oxygen consumption (VO2) were measured at rest and at the end of each workload. RESULTS: Systolic and diastolic BP were unrelated to catecholamines at rest and during exercise. When subjects were evaluated according to fitness level (VO2max), resting BP was not significantly different among groups (low fitness = VO2max < or = 25 ml/kg/min; moderate fitness = VO2max 26 to 39 ml/kg/min; high fitness = VO2max > or = 40 ml/kg/min). However, an inverse relationship was observed between fitness level and rate of rise of systolic and diastolic BP during submaximal work. Multiple regression showed that fitness predicted diastolic BP response (p = 0.02) at 100 watts. Age, however, predicted systolic BP response (p = 0.015). CONCLUSIONS: Neither the level of resting nor the magnitude of BP response to exercise in hypertensive subjects was directly related to level of plasma catecholamines. The magnitude of change in BP during exercise was modulated by age and fitness level.

Adult↗
PubMed1993

[Co-release of neuropeptides and catecholamines by adrenal medulla].

Different neuropeptides are costored together with catecholamines in the adrenal medulla. The concurrent release of these neuropeptides [neuropeptide Y (NPY), met-enkephalin (ME)] and catecholamines (adrenaline and noradrenaline) from the adrenal gland was examined in chloralose-anesthetized dogs after intravenous administration of dihydralazine (1 mg/kg) and insulin (0.3 U/kg). These results were compared to those obtained after the stimulation of the right splanchnic nerve at 1, 5 and 10 Hz frequencies. Baroreflex involvement or hypoglycemia induced a significant preferential increase in CA and ME versus basal values: around 16 fold for dihydralazine and 28 fold after insulin administration. In opposite, increase in NPY was only two times baseline. Splanchnic nerve stimulation induced a frequency-dependent increase in catecholamines and neuropeptides. At the lower frequencies (1 to 5 Hz), splanchnic nerve stimulation elicited a parallel increase in catecholamines and ME (13 to 17 fold basal values). By contrast, NPY increases 2 fold in the same conditions. At the higher frequencies (5 to 10 Hz), we observed a parallel (4 fold) increase in NA, ME and NPY adrenal plasma levels. In conclusion, the present data indicate that both adrenal ME and catecholamines (mainly NA) always exhibit a parallel fashion of corelease which is not the case for NPY and that different populations of chromaffin vesicles could be preferentially mobilized according to different physiological and pharmacological patterns.

Adrenal Medulla↗
PubMed1993

Do high fetal catecholamine levels affect heart rate variability and meconium passage during labour?

OBJECTIVES: To determine the relationship between umbilical arterial catecholamine levels and fetal heart rate variability and meconium passage. STUDY DESIGN: A prospective descriptive study was performed. Umbilical artery catecholamine levels were measured in 55 newborns and correlated with fetal heart rate before delivery, umbilical arterial pH, base excess and the presence of meconium-stained liquor. RESULTS AND CONCLUSION: The range of catecholamine levels was enormous, with very high epinephrine or norepinephrine levels in several fetuses. We were unable to demonstrate an association between high catecholamine levels and the presence of normal fetal heart rate variability despite acidaemia. We postulate that high catecholamine levels may inhibit fetal meconium passage.

Adolescent↗
PubMed1995

Bulbospinal catecholamine neurones and sympathetic pattern generation.

Populations of neurones containing noradrenaline, dopamine and possibly adrenaline project to the spinal cord where they innervate sympathetic preganglionic neurones (SPN). Studies are described which illustrate the actions of catecholamines on SPN and which suggest ways in which the catecholamine neurones could regulate the cardiovascular system. Experiments on rats using, intrathecal application of drugs to the spinal cord, iontophoresis, or superfusion of drugs whilst recording either postganglionic nerve activity, extracellularly or intracellularly from SPN respectively, reveal that catecholamines may excite or inhibit SPN. A slow depolarisation is mediated by alpha 1 adrenoceptors whereas alpha 2 adrenoceptors mediate a slow hyperpolarisation. Catecholamines may also excite glycinergic interneurones which elicit fast IPSPs in SPN. By regulating different ionic conductances in the membrane of SPN catecholamines are able to induce SPN to discharge tonically or to oscillate with bursts of action potentials. Furthermore these actions may be modified in the presence of an excitatory amino acid. It is suggested that via these mechanisms differential responses in the sympathetic outflow could be produced.

Animals↗
PubMedDate not supplied

Biosynthesis of catecholamines, uptake of 3H-noradrenaline, and reactivity of cardiovascular system of the rat after chronic and acute treatment with a new antidepressant agent, IPF C-45.

The effect of acute and chronic treatment of rats with IPF C-45 on the following biochemical and pharmacological parameters was tested: catecholamine concentration in brain, heart and adrenals, 3H-noradrenaline uptake by cardiac muscle, the action on catecholamine synthesis following treatment with alpha-methyl-p-tyrosine, reactivity of cardiovascular system to catecholamines and isoproterenol-induced tachycardia. Given chronically, IPF C-45 does not affect noradrenaline uptake by the cardiac muscle. Both chronic and acute administration of the drug decelerates catecholamine biosynthesis by inhibition of tyrosine hydroxylase activity. It seems that the action of IPF C-45, a benzonaphthyridone derivative, affects catecholamine metabolism in a manner distinctly different from that of tricyclic antidepressant drugs.

Adrenal Glands↗
PubMed1995

Effect of the pH and the importance of the internal standard on the measurement of the urinary catecholamines by high-performance liquid chromatography.

Clinical manifestations of phaeochromocytoma are not always sufficient for its early diagnosis. It is therefore necessary to confirm hypersecretion of catecholamines. Current methods for the measurement of catecholamines are based on their oxidative properties, and the majority of the laboratories often use HPLC methods for catecholamine testing. However, the extraction procedures used for the biogenic amines differ. We use a method of ion-exchange chromatography which is performed at pH 6.5. In order to avoid the spontaneous oxidation of the catecholamines, the urine samples has to be collected on HCl, which gives a pH of approximately 2. Occasionally, the acidified urine sample has a pH less than 1 requiring the addition of NaOH to reach a pH of 6.5, necessary for the adsorption of catecholamines on cation exchanger resins. This phenomenon produces a decrease in the peak areas but the use of an internal standard allows the final results to be corrected.

Catecholamines↗
PubMed1977

Inhibition of adrenal medullary catecholamine secretion by enflurane: II. Investigations in isolated bovine adrenals--site and mechanism of action.

To determine the site and mechanism of action underlying the inhibition of adrenal medullary catecholamine release by enflurane, the authors measured the effects of enflurane on catecholamine secretion evoked by various secretagogues in isolated bovine adrenals perfused with Locke's solution. Catecholamine concentrations in the perfusate were measured spectrofluorometrically. Enflurane caused concentration-dependent inhibition of catecholamine release in response to activation of the nicotinic receptors in the chromaffin cells with acetylcholine or dimethylphenylpiperazinium (DMPP). An enflurane concentration of 0.88 mM caused 50 per cent inhibition of the DMPP-induced secretion. The inhibition induced by enflurane was shown to be noncompetitive. The catecholamine release evoked by activation of the muscarinic receptors with pilocarpine was only slightly decreased by 3.74 mM enflurane. At this concentration the release in response to KCl, 56 mM, was partially inhibited, whereas the output in response to tyramine (from glands perfused with calcium-free Locke's solution) was unaffected. It is concluded that the site of action of enflurane is the cell membrane. At concentrations above 1 mM, enflurane may impair calcium ion influx, but at lower concentrations it probably interacts with hydrophobic regions of the nicotinic receptor.

Acetylcholine↗
PubMed1995

Regulation of calcium influx and catecholamine secretion in chromaffin cells by a cytochrome P450 metabolite of arachidonic acid.

These studies were designed to determine the role of arachidonic acid metabolites in catecholamine secretion from adrenal chromaffin cells. Inhibitors of the cytochrome P450-dependent metabolism of arachidonic acid were shown to interfere with stimulus-secretion coupling in cultured chromaffin cells. Ketoconazole (10 microM), clotrimazole (20 microM), and piperonyl butoxide (50 microM) inhibited carbachol-dependent catecholamine secretion by 44%, 83%, and 100%, respectively; histamine-dependent secretion by 25%, 60%, and 81%, and secretion induced by 59 mM KCl depolarization by 25%, 55%, and 89%. Uptake of 45Ca2+ into the cells in response to carbachol was inhibited 63% by ketoconazole, 86% by clotrimazole, and 95% by piperonyl butoxide; KCl-dependent uptake was inhibited 7%, 56%, and 85%, respectively. However, cytochrome P450 inhibitors did not inhibit catecholamine secretion when cells were stimulated with the calcium ionophores ionomycin or lasalocid. These results indicated the involvement of a cytochrome P450 product in controlling Ca2+ influx in response to membrane depolarization. Cells prelabeled with [3H]arachidonic acid formed a 3H-labeled metabolite which comigrated with authentic 5,6-epoxyeicosatrienoic (5,6-EET) acid on reverse phase and normal phase HPLC. Pretreatment with clotrimazole inhibited the production of this 3H-labeled metabolite. Addition of synthetic 5,6-EET (1 nM) to cells pretreated with piperonyl butoxide resulted in catecholamine secretion. These data suggest a role for a cytochrome P450 metabolite of arachidonic acid in agonist-stimulated catecholamine secretion.

8,11,14-Eicosatrienoic Acid↗
PubMed1996

Inhibition by protamine of catecholamine secretion and ion influxes in bovine adrenal medullary cells in culture.

To elucidate the mechanism of protamine-induced hypotension, we examined the effects of protamine on catecholamine secretion in bovine adrenal medullary cells and on the serum norepinephrine in the rat. 1) in bovine adrenal medullary cells in culture, protamine at concentrations of 10 to 100 micrograms/ml inhibited catecholamine secretion stimulated by carbachol. The inhibitory effect of protamine was diminished by heparin at concentrations of 3.5 to 14 U/ml. Protamine suppressed carbachol-stimulated 22Na+ influx and 45Ca++2 influx at a concentration similar to that which inhibited catecholamine secretion. Protamine (10-100 micrograms/ml) also inhibited veratridine-induced 22Na+ influx and 45Ca++ influx and 56 mM K(+)-evoked 45Ca++ influx. The inhibition of these ion influxes by protamine was closely correlated with that of catecholamine secretion. 2) In rats, i.v. administration of protamine (10 mg/kg) attenuated the arterial blood pressure and the serum norepinephrine. There was a high correlation (r = 0.96) between the serum norepinephrine and the arterial blood pressure in protaminetreated rats. Furthermore, pretreatment with heparin (1000 U/kg) abolished the protamine-induced decreases in arterial blood pressure and serum norepinephrine. Because protamine seems to inhibit catecholamine secretion by interfering with Na+ influx and Ca++ influx to adrenal medullary cells, the protamine-induced hypotension may be, at least in part, due to inhibition of norepinephrine release and ion channel activities of sympathetic nerve terminals in rats.

Adrenal Medulla↗
PubMed1997

The influence of endogenous catecholamines on the inhibitory effects of rolipram against early- and late-phase response to antigen in the guinea pig.

Selective inhibitors of the low-Km cAMP-specific phosphodiesterase (PDE4) inhibit inflammatory cell function and relax airway smooth muscle. Thus PDE4 inhibitors may be useful in the therapy of asthma. The present study was conducted to determine whether the in vivo activity of rolipram, a prototypical PDE4 inhibitor, is due to its ability to potentiate the anti-inflammatory effects of prostaglandins or catecholamines, endogenous activators of adenylyl cyclase, in models of the early- and late-phase response to antigen. Rolipram, administered i.v. to anesthetized, paralyzed and ventilated ovalbumin-sensitized guinea pigs, inhibited i.v. antigen-induced bronchoconstriction with an ID50 value of 0.2 mg/kg. Pretreatment with either of the beta adrenoceptor antagonists propranolol and nadolol (0.5 mg/kg i.v.), enhanced the bronchial reactivity to antigen and abolished the inhibitory activity of rolipram (0.1-10 mg/kg i.v.). In addition, the inhibitory activity of three structurally dissimilar PDE4 inhibitors was nearly abolished by propranolol. Cyclooxygenase inhibition by indomethacin slightly enhanced the reactivity to antigen but did not affect the inhibitory activity of rolipram. Plasma catecholamine concentrations were not altered by rolipram (0.3 or 1 mg/kg i.v.), which indicates that there was no stimulation of catecholamine release. Bilateral adrenalectomy reduced plasma epinephrine concentrations (from 1700 pg/ml to 400 pg/ml), significantly enhanced airway reactivity to antigen and substantially reduced the inhibitory activity of rolipram (3 mg/kg i.v.). Pretreatment of conscious guinea pigs with the beta adrenoceptor antagonist nadolol, 2 mg/kg p.o., enhanced aerosol antigen-induced bronchoconstriction and pulmonary eosinophil influx measured by bronchoalveolar lavage. Nadolol reduced the inhibitory effect of rolipram against antigen-induced bronchoconstriction but not eosinophil influx. The inhibitory effect of rolipram was unaffected by indomethacin. The present data suggest that circulating catecholamines play an important protective role against antigen-induced broncho-constriction in the guinea pig. Moreover, the inhibitory activity of PDE4 inhibitors against antigen-induced bronchoconstriction, but not eosinophil influx, is reduced by beta adrenergic blockade or adrenalectomy. Thus the inhibitory activity of PDE4 inhibitors against antigen-induced bronchoconstriction may be related to their synergism with endogenous catecholamines to suppress mast cell degranulation.

Adrenalectomy↗
PubMed1996

Potentiation by ouabain of catecholamine secretion from bovine adrenal chromaffin cells in culture induced by pituitary adenylate cyclase-activating polypeptide: evidence for involvements of Na+ and Ca2+ movements.

The effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on catecholamine secretion with ouabain, an inhibitor of Na(+)-K+ ATPase, in cultured bovine adrenal chromaffin cells was examined, to determine whether movement of Na+, as well as Ca2+, is involved in the secretory process. PACAP (10(-10)-10(-6)M)-induced catecholamine secretion was markedly potentiated by addition of ouabain (10(-5)M). When cultured cells were preincubated with PACAP for 30 min in Ca(2+)-free medium in the presence of ouabain and then stimulated for 15 min with Ca(2+)-containing medium without PACAP or ouabain, their catecholamine secretion was dependent on the external Ca2+ concentration, and 45Ca2+ influx into the cells was increased. When the cells had been preincubated with PACAP and ouabain in Na(+)-free sucrose medium, their Ca(2+)-induced catecholamine secretion was greatly reduced. PACAP increased 22Na+ influx into cells treated with ouabain. These results suggest that stimulation by PACAP and inhibition of the Na(+)-pump both increase the intracellular Na+ level, resulting in increase in Ca2+ influx and catecholamine secretion.

Adenylyl Cyclases↗