Inhibition of prostacyclin-induced Ca2+ mobilization by phorbol esters in Ob1771 preadipocytes.
In addition to cAMP production, a transient elevation of intracellular free Ca2+ has been shown to take place in preadipose cells upon stimulation by carbaprostacyclin (cPGI2), both messengers acting in synergy to initiate adipose cell differentiation (Vassaux, G., Gaillard, D., Ailhaud, G., and Négrel, R. (1992) J. Biol. Chem.267, 11092-11097). Further studies reported herein show that this Ca2+ transient is i) elicited by the natural prostaglandin PGI2, ii) independent of the presence of extracellular Ca2+, suggesting a mobilization of Ca2+ from intracellular pools and ii) unaffected by cAMP elevating agents. Moreover, and in contrast to the InsP3-dependent Ca2+ signal evoked by PGF2 alpha, that induced by PGI2 is fully abolished by pretreatment with phorbol esters (EC50: 1-5 nM). Furthermore, experiments designed to empty the Ca2+ pools, using PGI2 or PGF2 alpha as Ca2+ mobilizing agents as well as pretreatments with drugs, allow to conclude that PGI2 mobilizes Ca2+ from an InsP3 sensitive, ryanodine insensitive intracellular pool. Altogether, these results strongly suggest that PGI2 mobilizes Ca2+ from an intracellular store common to that affected by InsP3, by means of a mechanism which remains to be elucidated.
Vassaux
G
G
Centre de Biochimie, CNRS (UMR 134), Faculte des Sciences, Universite de Nice-Sophia Antipolis, France.
Far
D F
DF
Gaillard
D
D
Ailhaud
G
G
Negrel
R
R
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D010703:Phorbol Esters / Q000494:pharmacology*; D015290:Second Messenger Systems / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010703:Phorbol Esters; C026678:carboprostacyclin; D015237:Dinoprost; D011464:Epoprostenol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine