Differential regulation of thrombin- or ATP-induced mobilization of intracellular Ca2+ by prostacyclin receptor in mouse mastocytoma cells.
Thrombin induced an increase in [Ca2+]i in mouse mastocytoma P-815 cells. This increase was markedly reduced by prior exposure to pertussis toxin (PT) but not by removal of extracellular Ca2+, suggesting that thrombin stimulates phospholipase C via a PT-sensitive GTP-binding protein. ATP also induced an increase in [Ca2+]i. This increase was insensitive to PT but completely suppressed on removal of extracellular Ca2+, suggesting that ATP stimulates Ca2+ influx in a PT-insensitive manner. Iloprost, a stable prostacyclin analogue, increased the cellular cAMP level and dose-dependently inhibited the thrombin-induced increase in [Ca2+]i, whereas the ATP-induced increase in [Ca2+]i was markedly enhanced by iloprost. Cyclic AMP analogues, dibutyryl cAMP and 8-bromo cAMP, also inhibited the increase in [Ca2+]i induced by thrombin and promoted that by ATP, indicating that the inhibitory and stimulatory effects of iloprost are mediated by cAMP. These results suggest that the prostacyclin receptor differentially regulates two distinct Ca2+ mobilizing systems via cAMP in mastocytoma cells.
Negishi
M
M
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Hashimoto
H
H
Ichikawa
A
A
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000535:Aluminum / Q000494:pharmacology; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002712:Chlorides / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D016285:Iloprost / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D012515:Mast-Cell Sarcoma; D051379:Mice; D037342:Pertussis Toxin; D011453:Prostaglandins / Q000494:pharmacology*; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology*; D012969:Sodium Fluoride / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D017607:Aluminum Compounds; D002712:Chlorides; D011453:Prostaglandins; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D010566:Virulence Factors, Bordetella; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000077410:Aluminum Chloride; D015759:Ionomycin; D003994:Bucladesine; D000255:Adenosine Triphosphate; D012969:Sodium Fluoride; D000535:Aluminum; D011464:Epoprostenol; D000242:Cyclic AMP; D037342:Pertussis Toxin; D013917:Thrombin; D016285:Iloprost; D002118:Calcium