Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates the Synthesis of Dopamine in Cultured Bovine Adrenal Chromaffin Cells

抄録

The effect of pituitary adenylate cyclase-activating polypeptide_1-38 (PACAP_1-38) on the synthesis of dopamine in cultured bovine adrenal chromaffin cells was examined. PACAP_1-38 stimulated [¹⁴C]dopamine synthesis from [¹⁴C]tyrosine, in a concentration-dependent manner, causing maximal stimulation at 10^-7M. This stimulatory action of PACAP_1-38 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 Ca²⁺-free medium. PACAP_1-38 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 PACAP_1-38. These results indicate that PACAP_1-38 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. (Hypertens Res 1995; 18 Suppl. I: S169-S171)