Stimulatory 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.
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概要
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In cultured bovine adrenal chromaffin cells, pituitary adenylate cylase-activating polypeptide (PACAP) stimulated [<SUP>14</SUP>C]catecholamine synthesis from [<SUP>14</SUP>C]tyrosine (but not from [<SUP>14</SUP>C]DOPA) in a concentration-dependent manner, causing maximal stimulation at 10<SUP>-7</SUP> 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<SUP>2+</SUP>-free medium. PACAP (10<SUP>-7</SUP>M) increased the formation of [<SUP>3</SUP>H]inositol phosphates, [Ca<SUP>2+</SUP>]<SUB>i</SUB> and <SUP>45</SUP>Ca</SUP>2+</SUP> 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<SUP>+</SUP>, which activates Ca<SUP>2+</SUP> uptake, were further enhanced by PACAP, suggesting that both cAMP- and Ca<SUP>2+</SUP>-dependent protein kinases may be involved in the stimulation of tyrosine hydroxylase phosphorylation and catecholamine synthesis caused by PACAP.
- 公益社団法人 日本薬理学会の論文
著者
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Hamano Shuichi
Department of Pathological Science and Technology, The Institute of Health Bioscience, The Universit
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Houchi Hitoshi
Department Of Pharmacology The University Of Tokushima School Of Medicine
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OHUCHI Takeshi
Department of Forest and Forest Products Sciences Fuculty of Agriculture Kyushu Unviversity
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OKA Motoo
Department of Pharmacology II, Osaka University School of Medicine
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Masuda Yutaka
Deparmtent Of Cardiovascular Surgery Institute Of Health Biosciences University Of Tokushima Graduat
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Azuma Mami
Department of Pharmacology, Tokushima University School of Medicine
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HOUCHI Hitoshi
Department of Pharmacology, Tokushima University School of Medicine
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Ishimura Yasuko
Department of Pharmacology, Tokushima University School of Medicine
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