INDUCTION OF CALCIUM-RELEASE FROM ISOLATED SARCOPLASMIC-RETICULUM BY TRIPHENYLTIN

A direct peripheral myopathy has been found in organotin intoxication and suggested to be a significant factor in the development of muscle weakness following exposure, In this study, by using the isolated sarc oplasmic reticulum membrane vesicles, we have shown that triphenyltin dose-dependently induced Ca2+ release from the actively and passively loaded sarcoplasmic reticulum vesicles, Triphenyltin induced Ca2+ rele ase in ruthenium red-sensitive and insensitive ways with EC50 values o f 75 and 270 mu M, respectively, The Ca2+-ATPase activity and Ca2+ upt ake of sarcoplasmic reticulum were also inhibited by triphenyltin. Tri phenyltin exerted dual effects on the apparent [H-3]ryanodine binding. Triphenyltin (0.5-10 mu M) dose-dependently potentiated the [H-3]ryan odine binding; however, the [H-3] ryanodine binding decreased as the c oncentration of triphenyltin increased, The dissociation of bound [H-3 ] ryanodine was facilitated by triphenyltin. The present study suggest ed that the internal Ca2+ store of skeletal muscle could be depleted b y triphenyltin through the inhibition of the Ca2+ uptake and the induc tion of Ca2+ release by acting on the Ca2+-ATPase and Ca2+ release cha nnel, also known as the ryanodine receptor, of sarcoplasmic reticulum, respectively, These results could partly explain the development of m uscle weakness in organotin intoxication; however, their relevance to the development of peripheral myopathy requires further examination.