Catecholamine secretion, adrenal

Pituitary Adenylyl Cyclase-activating Polypeptide (PACAP) is a 38-amino acid peptide (PACAP-38), which is widely expressed in the central nervous system. PACAP is most abundant in the hypothalamus. It is also found in the gastrointestinal tract, the adrenal gland and in testis. Its central nervous system functions are ill-defined. In the periphery, PACAP has been shown to stimulate catecholamine secretion from the adrenal medulla and to regulate secretion from the pancreas. Three G-protein coupled receptors have been shown to respond to PACAP, PAQ (PACAP type I) specifically binds PACAP, VPACi and VPAC2 also bind vasoactive intestinal peptide (VDP). Activation of PACAP receptors results in a Gs-mediated activation of adenylyl cyclase. 

Liu PS, Kao LS, Lin MK. 1994. Organophosphates inhibit catecholamine secretion and calcium influx in bovine adrenal chromaffin cell. Toxicology 90 81-91. 

The adrenal gland is located on the upper segment of the kidney (Fig. 42-1). It consists of an outer cortex and an inner medulla. The adrenal medulla secretes the catecholamines epinephrine (also called adrenaline) and norepineprhine (also called noradrenaline), which are involved in regulation of the sympathetic nervous system. The adrenal cortex consists of three histologically distinct zones zona glomerulosa, zona fasciculata, and an innermost layer called the zona reticularis. Each zone is responsible for production of different hormones (Fig. 42-2). 

The major circulating hormones that influence vascular smooth muscle tone are the catecholamines epinephrine and norepinephrine. These hormones are released from the adrenal medulla in response to sympathetic nervous stimulation. In humans, 80% of catecholamine secretion is epinephrine and 20% is norepinephrine. Stimulation of cy-adrenergic receptors causes vasoconstriction. The selective a,-adrenergic receptor antagonist, prazosin, is effective in management of hypertension because it causes arterial and venous smooth muscle to relax. 

Adrenal gland A triangle-shaped organ positioned at the top of the kidney which functions as a double endocrine gland . The larger outer adrenal cortex secretes three classes of steroid hormones glucocorticoids (e.g., cortisol), minerlocorticoids (aldosterone) and small amounts of sex steroids (e.g., testosterone). The inner adrenal medulla secretes catecholamines (e.g., adrenaline and noradrenaline). 

Neurotensin-induced adrenal chromaffin cell catecholamine secretion] NEUT-R antagonist (CPA) [inhibits mast cell Histamine release]... 

Histamine, serotonin and the catecholamines (dopamine, epinephrine and norepinephrine) are synthesized from the aromatic amino acids histidine, tryptophan and phenylalanine, respectively. The biosynthesis of catecholamines in adrenal medulla cells and catecholamine-secreting neurons can be simply summarized as follows [the enzyme catalysing the reaction and the key additional reagents are in square brackets] phenylalanine — tyrosine [via liver phenylalanine hydroxylase + tetrahydrobiopterin] —> i.-dopa (l.-dihydroxyphenylalanine) [via tyrosine hydroxylase + tetrahydrobiopterin] —> dopamine (dihydroxyphenylethylamine) [via dopa decarboxylase + pyridoxal phosphate] — norepinephrine (2-hydroxydopamine) [via dopamine [J-hydroxylasc + ascorbate] —> epinephrine (jV-methyl norepinephrine) [via phenylethanolamine jV-methyltransferase + S-adenosylmethionine]. 

Dar, D.E., and Zinder, O. 1998. Catecholamine secretion from bovine adrenal chromaffin cells induced by the dextrorotatory isomer of anatoxin-a. Gen Pharmacol 31, 737-740. 

Ahnert-Hilger G, Bader MF, BhakDai S et al. (1989b) Introduction of macromolecules into bovine adrenal medullary chromaffin cells and rat pheochromocy-toma cells (PC12) by permeabilization with streptolysin O inhibitory effect of tetanus toxin on catecholamine secretion. J. Neurochem. 52 1751 -8... 

Camphor inhibited catecholamine secretion from bovine adrenal chromaffin cells. 

Membrane Stabilization. Calcium not only mediates secretion, but it also "stabilizes cell membranes, making it more difficult for calcium to enter cells. For example, if adrenal medulla is stimulated with 100 yg/ml of acetylcholine (the physiological neurotransmitter) at various calcium concentrations, catecholamine secretion increases as calcium increases up to at least 17.6 mM calcium (9). By contrast, pancreatic insulin secretion in response to glucose, peaks at 5.5 mM calcium and falls off at calcium concentrations on either side of the peak (10). So the relation between calcium concentration in the medium and the extent of secretion varies with the tissue and depends on the degree of membrane stabilization by calcium, a factor which influences the amount of calcium entering secretory cells. 

The catecholamines epinephrine and norepinephrine (adrenaline and noradrenaline) originate in the inner medullar region of the adrenal glands. Stimulation of the adrenal by the sympathetic nervous system leads to secretion of catecholamines into the bloodstream. In addition, adipose tissue is itself directly innervated by the sympathetic nervous system. Various types of metabolic stress trigger the sympathetic nervous system to release its neurotransmitter, norepinephrine, directly into adipose where its effects on the adipocyte are mediated by specific plasma membrane adrenoreceptors. Rapid reflex responses are primarily stimulated by the sympathetic nervous system, whereas more long-term (i.e., on the scale of hours, days, and weeks) and/or basal effects are subject to regulation by catecholamine secretion. 

Another study has shown a significant association between the severity of pulmonary inflammation/fibrosis induced by IP, as well as other particulate compounds including nickel oxide, nickel subsulfide, cobalt sulfate, and talc, and increased incidences of adrenal pheochromocytoma in rats (Ozaki et al. 2002). The systemic hypoxemia and reduced gas exchange induced by chronic pulmonary lesions from IP exposures may result from stimulated catecholamine secretion from the adrenal medulla and this chronic endocrine hyperactivity may lead to hyperplasia and neoplasia of the adrenal gland. 

Use of tricyclics in the presence of catecholamine-secreting tumors of the adrenal medulla (e.g., pheochromocytoma, neuroblastoma), may precipitate a hypertensive crisis, due to the increase in catecholamine production in the face of decreased adrenergic reuptake. 

ARBs potently and selectively inhibit most of the biological effects of Angll, including Angll-induced (1) contraction of vascular smooth muscle, (2) rapid pressor responses, (3) slow pressor responses, (4) thirst, (5) vasopressin release, (6) aldosterone secretion, (7) release of adrenal catecholamines, (8) enhancement of noradrenergic neurotransmission, (9) increases in sympathetic tone, (10) changes in renal function, and (11) cellular hypertrophy and hyperplasia. 

M. Herrera, L. S. Kao, D. J. Curran, and E. W. Westhead, Flow-Injection Analysis of Catecholamine Secretion from Bovine Adrenal Medulla Cells on Microbeads. Anal. Biochem., 144 (1985) 218. 

K -evoked catecholamine secretion from bovine chromafhn cells is greatly potentiated in the presence of the DHP L-type channel agonist Bay K 8644 the rise in secretion parallels the increase in " Ca uptake [165]. Cena et al. [166] showed that nitrendipine completely blocked catecholamine release ([ H]-norepinephrine) in bovine chromafhn cells stimulated with high K". These results do not agree with those obtained by other authors who found that in bovine chromafhn cells, DHP did not block more than 40-50% of the secretion [167-169]. The differences may be based on different stimulation patterns and the use of cultured chromafhn cells, fast superfused cell populations, or the intact perfused adrenal gland. 

Kitamura et al. [63] have studied the effects of co-conotoxin GVIA and L-type Ca channel blockers (nifedipine and verapamil) on catecholamine release in anesthetized dogs. Catecholamine release into the blood stream was induced either by electrical stimulation of the splanchnic nerve or by intra-arterial injection of acetylcholine. Administration of 0.4 pg/mL of co-conotoxin GVIA reduced catecholamine secretion by 30% in response to the electrical stimulation nifedipine or verapamil had no effect under these experimental conditions. However, when catecholamine release was induced by acetylcholine, co-conotoxin GVIA blocked secretion by around 50% and nifedipine also reduced it by 50%. These results suggest that N- and L-type Ca channels contribute to the release of catecholamines in the dog adrenal gland. To our knowledge, a patch-clamp study that determines the subtypes of Ca channels expressed by dog chromaffin cells is not available. 

O Farrell M, Ziogas J, Marley RD. Effects of N- and L-type calcium chaimel antagonists and (-l-/-)-Bay K8644 on nerve-induced catecholamine secretion from bovine perfused adrenal glands. Br J Pharmacol 1997 121(3) 381-8. 

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