Houchi H, Azuma M, Kitamura K, Okuno M, Oka M
Department of Pharmacology, Tokushima University School of Medicine, Japan.
Hypertens Res. 1995 Jun;18 Suppl 1:S169-71. doi: 10.1291/hypres.18.supplementi_s169.
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.
研究了垂体腺苷酸环化酶激活多肽1 - 38（PACAP1 - 38）对培养的牛肾上腺嗜铬细胞中多巴胺合成的影响。PACAP1 - 38以浓度依赖的方式刺激[¹⁴C]酪氨酸合成[¹⁴C]多巴胺，在10⁻⁷M时产生最大刺激作用。PACAP1 - 38的这种刺激作用不受星形孢菌素（蛋白激酶C抑制剂）的显著抑制，也不受长期暴露于TPA（蛋白激酶C激活剂）导致蛋白激酶C下调的细胞的影响，而在无钙培养基中其作用部分减弱。PACAP1 - 38增加了[³H]肌醇磷酸的形成、细胞内钙离子浓度（[Ca²⁺]i）、⁴⁵Ca²⁺摄取和环磷酸腺苷（cAMP）水平。该肽还刺激了酪氨酸羟化酶的磷酸化，酪氨酸羟化酶是催化多巴胺合成限速步骤的酶。由二丁酰环磷腺苷（dibutyryl cAMP）的最大有效浓度或高钾（激活Ca²⁺摄取）刺激的多巴胺合成和酪氨酸羟化酶磷酸化，被PACAP1 - 38进一步增强。这些结果表明，PACAP1 - 38可能刺激培养的牛肾上腺嗜铬细胞中环磷酸腺苷依赖性蛋白激酶和钙依赖性蛋白激酶的活性，可能通过刺激酪氨酸羟化酶的磷酸化导致多巴胺合成增加。
