title: Caffeine inhibits Ca(2+)-mediated potentiation of inositol 1,4,5-trisphosphate-induced Ca2+ release in permeabilized vascular smooth muscle cells.
abstract: We studied the effects of caffeine on inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release in saponin-permeabilized smooth muscle cells. The Ca2+ concentration in the vicinity of the Ca2+ store was strongly buffered to exclude the secondary effect of Ca2+ on the Ca2+ release. 2 mM caffeine shifted the IP3 concentration-Ca2+ release relation at 100 nM Ca2+ to the higher IP3 concentration without decreasing the steepness of the relation. The ascending limb of the biphasic Ca2+ dependence of IP3-induced Ca2+ release was shifted to the higher Ca2+ concentration by 2 mM caffeine. However, caffeine showed little inhibitory effect in the absence of Ca2+. These results indicate that caffeine inhibits IP3-induced Ca2+ release only when the Ca2+ release is potentiated by Ca2+.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hirose
authors.forename: M
authors.initials: M
authors.lastname: Iino
authors.forename: M
authors.initials: M
authors.lastname: Endo
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium