Ruthenium red selectively prevents Ins(1,4,5)P3-but not caffeine-gated calcium release in avian atrium.
We previously reported that inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and caffeine evoked contractures in saponin-permeabilized chick atria. The magnitude of contractures evoked by maximally effective concentrations of Ins(1,4,5)P3 were half those evoked by maximally effective concentrations of caffeine. In the present report, we tested the hypothesis that these two agents may act on distinct calcium-release mechanisms by comparing the effects of ryanodine, ruthenium red, and procaine on the responses to Ins(1,4,5)P3 and caffeine. We find that procaine inhibits both responses with similar mean inhibitory concentrations in the millimolar range. Nanomolar concentrations of ryanodine selectively potentiate the contractures induced by Ins(1,4,5)P3 but have no effect on those induced by caffeine. Micromolar concentrations of ryanodine inhibit responses to both Ins(1,4,5)P3 and caffeine in a use-dependent way. Ruthenium red prevents the response to Ins(1,4,5)P3 and potentiates that to caffeine, as if ruthenium red had enhanced calcium accumulation in the caffeine-sensitive pool(s). Because we found that caffeine prevented the subsequent response to Ins(1,4,5)P3, but Ins(1,4,5)P3 had no detectable effect on the caffeine-induced contracture, we conclude that Ins(1,4,5)P3 and caffeine act on pharmacologically distinct calcium-release mechanisms that may reside in the same sarcoplasmic reticulum compartment.
Vites
A M
AM
Department of Pharmacology, University of Connecticut Health Center, Farmington 06030.
Pappano
A J
AJ
D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D015640:Ion Channel Gating; D009206:Myocardium / Q000378:metabolism*; D009994:Osmolar Concentration; D011343:Procaine / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology*; D012433:Ryanodine / Q000494:pharmacology
D012430:Ruthenium Red; D012433:Ryanodine; D002110:Caffeine; D011343:Procaine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium