CAFFEINE AND CARBACHOL ACT ON COMMON CA2+ STORES TO RELEASE CA2+ IN GUINEA-PIG ILEAL SMOOTH-MUSCLE

To characterize intracellular Ca2+ stores, the Ca2+-releasing effects of caffeine, carbachol and inositol 1,4,5-trisphosphate (IF3) were compared by measuring the drug-induced tension development in beta-escin-skinned longitudinal smooth muscle of guinea-pig ileum. Caffeine (20 mM), carbachol (10 or 100 mu M) or IF3 (40 mu M), applied after loading Ca2+ within intracellular stores, produced a transient rise in tension in a Ca2+-free solution. This change in tension occurred in response to release of Ca2+ from the stores. The effect of either caffeine or carbachol was markedly reduced or abolished after preceding application of the other drug. IF3 was without effect when applied subsequently to caffeine. The effects of carbachol and IF3 were abolished after combined treatment with ryanodine (30 mu M) and caffeine (20 mM) which causes functional removal of caffeine-releasable Ca2+ stores, but not after combined treatment with ryanodine (30 mu M) and carbachol (10 mu M). The results suggest that caffeine, carbachol and IF3 all act on common Ca2+ stores to release Ca2+.