Pituitary adenylate cyclase-activating polypeptide stimulates the synthesis of dopamine in cultured bovine adrenal chromaffin cells.
The effect of pituitary adenylate cyclase-activating polypeptide1-38 (PACAP1-38) on the synthesis of dopamine in cultured bovine adrenal chromaffin cells was examined. PACAP1-38 stimulated [14C]dopamine synthesis from [14C]tyrosine, in a concentration-dependent manner, causing maximal stimulation at 10(-7)M. This stimulatory action of PACAP1-38 was not significantly inhibited 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. PACAP1-38 increased the formation of [3H] inositol phosphates, [Ca2+]i, 45Ca2+ uptake and cAMP level. The peptide also stimulated the phosphorylation of tyrosine hydroxylase, the enzyme catalyzing the rate-limiting step in dopamine synthesis. Dopamine 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 PACAP1-38. These results indicated that PACAP1-38 may stimulate the activities of cAMP- and calcium-dependent protein kinases in cultured bovine adrenal chromaffin cells, resulting in increase in the synthesis of dopamine probably by stimulation of phosphorylation of tyrosine hydroxylase.
Department of Pharmacology, Tokushima University School of Medicine, Japan.
H
H
Houchi
M
M
Azuma
K
K
Kitamura
M
M
Okuno
M
M
Oka
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000096:biosynthesis*; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010766:Phosphorylation; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D013268:Stimulation, Chemical; D014443:Tyrosine / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014443:Tyrosine; D014446:Tyrosine 3-Monooxygenase; D011493:Protein Kinase C; D002118:Calcium; D004298:Dopamine