Open AccessStimulatory Effect of Pituitary Adenylate Cyclase-Activating Polypeptide on Catecholamine Synthesis in Cultured Bovine Adrenal Chromaffin Cells: Involvements of Tyrosine Hydroxylase Phosphorylation Caused by Ca2+ Influx and cAMP
Author(s) -
Hitoshi Hishida,
Shuichi Hamano,
Yutaka Masuda,
Yasuko Ishimura,
Mami Azuma,
Tomoyuki Ohuchi,
M. Oka
Publication year - 1994
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.66.323
Subject(s) - pituitary adenylate cyclase activating peptide , tyrosine hydroxylase , adenylate kinase , chromaffin cell , phosphorylation , catecholamine , adrenal medulla , protein kinase a , endocrinology , medicine , tyrosine 3 monooxygenase , tyrosine phosphorylation , tyrosine , chemistry , cyclase , kinase , biology , stimulation , biochemistry , enzyme , dopamine , vasoactive intestinal peptide , receptor , neuropeptide
In cultured bovine adrenal chromaffin cells, pituitary adenylate cylase-activating polypeptide (PACAP) stimulated [14C]catecholamine synthesis from [14C]tyrosine (but not from [14C]DOPA) in a concentration-dependent manner, causing maximal stimulation at 10(-7) M. The stimulatory action of PACAP was not affected by staurosporine (an inhibitor of protein kinase C) or in the cells in which protein kinase C was down-regulated by prolonged exposure to TPA (an activator of protein kinase C), whereas it was partially attenuated in Ca(2+)-free medium. PACAP (10(-7) M) increased the formation of [3H]inositol phosphates, [Ca2+]i and 45Ca2+ uptake as well as cAMP. The peptide also stimulated the phosphorylation of tyrosine hydroxylase, the enzyme catalyzing the rate-limiting step in catecholamine synthesis. Catecholamine synthesis and tyrosine hydroxylase phosphorylation stimulated by the maximal effective concentration of dibutyryl cAMP or high K+, which activates Ca2+ uptake, were further enhanced by PACAP, suggesting that both cAMP- and Ca(2+)-dependent protein kinases may be involved in the stimulation of tyrosine hydroxylase phosphorylation and catecholamine synthesis caused by PACAP.