[Possible role of a neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) on stimulus-secretion coupling in catecholamine neuron].
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide first isolated from ovine hypothalamic tissue. This peptide stimulates adenylate cyclase activation. However, few details were known of the function of this peptide on stimulus-secretion coupling in neuronal cells. The authors have investigated the role of PACAP on catecholamine biosynthesis and secretion using cultured bovine adrenal chromaffin cells as a model for catecholamine-containing neurons. PACAP38, the 38-amino acid form of PACAP, increased cAMP formation in bovine adrenal chromaffin cells. In addition, PACAP38 increased [Ca2+]i associated with PI turnover and Ca2+ influx into the cells. The synthesis of catecholamine and the phosphorylation of tyrosine hydroxylase, a rate-limiting enzyme of catecholamine biosynthesis, stimulated by the maximal effective concentration of dibutyryl cAMP or a high concentration (56 mM) of K+ were further enhanced by PACAP38. Thus PACAP38 stimulated the pathway of catecholamine biosynthesis mainly by both activation of cAMP- and Ca2(+)-dependent protein kinases. On catecholamine secretion from the cells, the effect of PACAP38 was markedly potentiated by addition of ouabain, an inhibitor of Na+/K+ ATPase. This markedly potentiated secretion was greatly reduced with Na+ omitted-sucrose medium. PACAP38 increased 22Na+ influx into the cells treated with ouabain. Thus PACAP38 with ouabain stimulated catecholamine secretion by accumulation of intracellular Na+, resulting in an increase in Ca2+ influx. These results indicate that the neuropeptide PACAP has an important role in stimulus-secretion coupling in adrenal chromaffin cells.
Azuma
Mami
M
Division of Pharmacy, Tokushima University Hospital, 2-50-1, Kuramoto-cho, Tokushima 770-8503, Japan. mamichan@clin.med.tokushima-u.ac.jp
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000096:biosynthesis / Q000378:metabolism*; D002417:Cattle; D019439:Chromaffin Cells / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D010766:Phosphorylation; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011494:Protein Kinases / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010042:Ouabain; D012964:Sodium; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D011494:Protein Kinases; D002118:Calcium