Two types of prostacyclin receptor coupling to stimulation of adenylate cyclase and phosphatidylinositol hydrolysis in a cultured mast cell line, BNu-2cl3 cells.
Prostacyclin (PGI2)-mediated signal transduction was examined in interleukin 3 (IL-3)-dependent BNu-2cl3 mast cells. Iloprost, a stable PGI2 analogue, induced the accumulation of intracellular cAMP and IP3, and an increase in the intracellular Ca2+ concentration. Pretreatment of the cells with a protein kinase C activator, 12-O-tetradecanoyl phorbol 13-acetate, suppressed the iloprost-induced IP3 accumulation and Ca2+ mobilization, but inversely potentiated the cAMP accumulation, suggesting that neither of these signal transduction pathways of iloprosts is the result of a secondary effect of activation of the other. Removal of IL-3 from the culture medium reduced the iloprost-induced IP3 accumulation and Ca2+ mobilization, while it had no effect on the iloprost-induced cAMP accumulation at all. These results taken together suggest that BNu-2cl3 cells express two types of PGI2 receptor; one couples to stimulation of adenylate cyclase, its expression being independent of IL-3, while the other couples to phosphatidylinositol hydrolysis, its expression being dependent on IL-3.
Oka
M
M
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Negishi
M
M
Nishigaki
N
N
Ichikawa
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D011464:Epoprostenol / Q000378:metabolism; D006868:Hydrolysis; D016285:Iloprost / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007377:Interleukin-3 / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010716:Phosphatidylinositols / Q000378:metabolism*; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007377:Interleukin-3; D010716:Phosphatidylinositols; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D015544:Inositol 1,4,5-Trisphosphate; D011464:Epoprostenol; D000262:Adenylyl Cyclases; D016285:Iloprost; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium