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.
Hasegawa
T
T
Department of Community Health Science, Saga Medical School, Japan.
Kumagai
S
S
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000494:pharmacology*; D007700:Kinetics; D009132:Muscles / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011898:Ranidae; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D013403:Sugar Phosphates / Q000494:pharmacology*
D007295:Inositol Phosphates; D013403:Sugar Phosphates; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D000527:Alprostadil; D002118:Calcium; D007213:Indomethacin