ATP Receptor-Mediated Increase of Ca Ionophore-Stimulated Arachidonic Acid Release from PC12 Pheochromocytoma Cells

The Japanese Journal of Pharmacology

Toshihiko Murayama¹  Yasuyuki Nomura¹  Haruko Oda¹  Asako Watanabe¹ 

[1] Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University

关键词: ATP;    Arachidonic acid;    Intracellular calcium;    PC12 cell;   

DOI  :  10.1254/jjp.69.43

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(39)Cited-By(13)Phospholipase A2 has recently been proposed as the effector enzyme involved in the receptor-mediated release of arachidonic acid (AA). Released AA and its metabolites have been demonstrated to play an important role in the regulation of cell functions. [3H]AA release from prelabeled PC12 cells was stimulated by a Ca ionophore such as ionomycin or A23187. Although ATP and its effective analogs, adenosine 5’-O-(3-thiotrisphosphate) (ATPγS), 2-methylthio ATP and 3’-O-(4-benzoyl)benzoyl ATP, did not stimulate [3H]AA release on their own, they did enhance Ca ionophore-stimulated [3H]AA release. The effect of ATP analogs was dose-dependent. ADP, UTP, GTP, ITP, αβ3-methylene ATP, βγ-methylene ATP and 8-bromo ATP showed no effect or very limited effect. The effect of ATPγS was antagonized by suramin, a putative P2Y receptor antagonist. The effective ATP analogs also increased [Ca2+], (cytosolic free Ca2+ concentration) via Ca 2+ influx. However, the addition of 50 mM KCl or 10 μM bradykinin, which are well-known to increase [Ca2+]; by different pathways, did not stimulate [3H]AA release, either with or without the Ca ionophore. The addition of phorbol 12-myristate 13-acetate, an activator of protein kinase C, showed no effect on [3H]AA release, either with or without the Ca ionophore. These data suggest that 1) ATP increased Ca ionophore-stimulated AA release via a P2Y-like ATP receptor, and that 2) the elevation of [Ca2+]; by ATP does not quantitatively explain the ATP-stimulated AA release in PC12 cells.

【 授权许可】

Unknown