Cross-talk between Ca2+ influx and phosphoinositide hydrolysis by extracellular adenosine triphosphate in rat PC12 pheochromocytoma cells.
In rat PC12 pheochromocytoma cells, extracellular ATP stimulated 45Ca2+ influx even in the presence of nifedipine, a Ca2+ antagonist that inhibits the voltage-dependent L-type Ca2+ channel, and stimulated the formation of inositol trisphosphate (IP3). The effect of ATP on 45Ca2+ influx was more potent than that on the formation of IP3 at a dose lower than 0.1 mM. 12-O-Tetradecanoylphorbol-13-acetate, a protein kinase-C (PKC)-activating phorbol ester, which by itself had little effect on 45Ca2+ influx, significantly reduced the ATP-induced 45Ca2+ influx in a dose-dependent manner in the range between 1 nM and 0.1 microM. However, 4 alpha-phorbol 12, 13-didecanoate, a PKC-nonactivating phorbol ester, had little effect on the 45Ca2+ influx induced by ATP. Staurosporine, an inhibitor for PKC, significantly enhanced the ATP-induced 45Ca2+ influx. Pertussis toxin inhibited the ATP-induced formation of IP3 in a dose-dependent manner in the range between 0.1 ng/ml and 1 microgram/ml. On the other hand, pertussis toxin significantly enhanced the ATP-induced 45Ca2+ influx. These results strongly suggest that extracellular ATP-induced Ca2+ influx is autoregulated due to the activation of PKC resulting from pertussis toxin-sensitive GTP-binding protein-coupled phosphoinositide hydrolysis in PC12 pheochromocytoma cells.
Department of Biochemistry, Institute for Developmental Research, Aichi Prefectural Colony (O.K.), Japan.
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Kozawa
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Miwa
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Tokuda
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D006868:Hydrolysis; D007700:Kinetics; D009543:Nifedipine / Q000494:pharmacology; D016716:PC12 Cells / Q000378:metabolism*; D037342:Pertussis Toxin; D010703:Phorbol Esters / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000470:Alkaloids; D002132:Calcium Radioisotopes; D010703:Phorbol Esters; D010716:Phosphatidylinositols; D010566:Virulence Factors, Bordetella; C008876:phorbol-12,13-didecanoate; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019311:Staurosporine; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium