A G-protein of sarcoplasmic reticulum of skeletal muscle is activated by caffeine or inositol trisphosphate

Here we show the activation of G-protein by inositol trisphosphate (IP₃) or caffeine in sarcoplasmic reticulum (SR) of skeletal muscle and the consequent existence of a common mechanism of Ca²⁺ release from SR induced by caffeine and by IP₃. (i) Indomethacin inhibits Ca²⁺ release induced by IP₃ or caffeine. (ii) PGE₁ does not induce Ca²⁺ release itself, but does stimulate Ca²⁺ release induced by IP₃, or caffeine, from SR. (iii) Forskolin stimulates both types of Ca²⁺ release. The inhibitory effect of indomethacin on both forms of Ca²⁺ release, and the stimulatory effect of PGE₁ and forskolin on either Ca²⁺ release suggest that there exists a common mechanism between IP₃- and caffeine-induced Ca²⁺ release. (iv) Caffeine or IP₃ activates G-protein via inhibition of a GTPase activity. (v) Indomethacin itself inactivates this G-protein by stimulation of a GTPase activity and reverses the activation of G-protein induced by IP₃ or caffeine. (vi) PGE₁ competes with the inhibitory effect of indomethacin on GTPase activity and PGE₁ itself activates G-protein through inhibition of GTPase activity. From these results, it could be suggested that caffeine or IP₃ induces Ca²⁺ release from the SR via activation of G-protein, which affects the Ca²⁺ channel and cAMP which seems to affect G-protein via A-kinase.