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

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著者

    • HOUCHI Hitoshi
    • Department of Pharmacology, Tokushima University School of Medicine
    • AZUMA Mami
    • Department of Pharmacology, Tokushima University School of Medicine
    • OKUNO Masaaki
    • Department of Pharmacology, Tokushima University School of Medicine
    • OKA Motoo
    • Department of Pharmacology, Tokushima University School of Medicine

抄録

The effect of pituitary adenylate cyclase-activating polypeptide<sub>1-38</sub> (PACAP<sub>1-38</sub>) on the synthesis of dopamine in cultured bovine adrenal chromaffin cells was examined. PACAP<sub>1-38</sub> stimulated [<sup>14</sup>C]dopamine synthesis from [<sup>14</sup>C]tyrosine, in a concentration-dependent manner, causing maximal stimulation at 10<sup>-7</sup>M. This stimulatory action of PACAP<sub>1-38</sub> 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<sup>2+</sup>-free medium. PACAP<sub>1-38</sub> increased the formation of [<sup>3</sup>H] inositol phosphates, [Ca<sup>2+</sup>]i, <sup>45</sup>Ca<sup>2+</sup> 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<sup>+</sup>, which activates Ca<sup>2+</sup> uptake, were further enhanced by PACAP<sub>1-38</sub>. These results indicate that PACAP<sub>1-38</sub> 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. (<i>Hypertens Res</i> 1995; 18 Suppl. I: S169-S171)

収録刊行物

  • Hypertension research : clinical and experimental : official journal of the Japanese Society of Hypertension

    Hypertension research : clinical and experimental : official journal of the Japanese Society of Hypertension 18, S169-S171, 1995-06-01

    The Japanese Society of Hypertension

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