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 sarcoplasmic reticulum membrane vesicles, we have shown that triphenyltin dose-dependently induced Ca 2+ release from the actively and passively loaded sarcoplasmic reticulum vesicles. Triphenyltin induced Ca 2+ release in ruthenium red-sensitive and insensitive ways with EC 50 values of 75 and 270 μM, respectively. The Ca 2+-ATPase activity and Ca 2+ uptake of sarcoplasmic reticulum were also inhibited by triphenyltin. Triphenyltin exerted dual effects on the apparent [ 3H]ryanodine binding. Triphenyltin (0.5-10 μM) dose-dependently potentiated the [ 3H]ryanodine binding; however, the [ 3H] ryanodine binding decreased as the concentration of triphenyltin increased. The dissociation of bound [ 3H] ryanodine was facilitated by triphenyltin. The present study suggested that the internal Ca 2+ store of skeletal muscle could be depleted by triphenyltin through the inhibition of the Ca 2+ uptake and the induction of Ca 2+ release by acting on the Ca 2+-ATPase and Ca 2+ release channel, also known as the ryanodine receptor, of sarcoplasmic reticulum, respectively. These results could partly explain the development of muscle weakness in organotin intoxication; however, their relevance to the development of peripheral myopathy requires further examination.
|Number of pages||5|
|Journal||Journal of Biochemistry|
|Publication status||Published - Jul 1997|
- Ca release
- Sarcoplasmic reticulum
- Skeletal muscle
ASJC Scopus subject areas