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.
Houchi
H
H
Department of Pharmacology, Tokushima University School of Medicine, Japan.
Azuma
M
M
Kitamura
K
K
Okuno
M
M
Oka
M
M
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