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 sarcoplasmic 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+ release in ruthenium red-sensitive and insensitive ways with EC50 values of 75 and 270 microM, respectively. The Ca2+-ATPase activity and Ca2+ uptake of sarcoplasmic reticulum were also inhibited by triphenyltin. Triphenyltin exerted dual effects on the apparent [3H]ryanodine binding. Triphenyltin (0.5-10 microM) 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 Ca2+ store of skeletal muscle could be depleted by triphenyltin through the inhibition of the Ca2+ uptake and the induction of Ca2+ release by acting on the Ca2+-ATPase and Ca2+ 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.
Kang
J J
JJ
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei. jjkang@ccms.ntu.edu.tw
Chen
I L
IL
Cheng
Y W
YW
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism; D009947:Organotin Compounds / Q000494:pharmacology*; D011817:Rabbits; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D012834:Silver / Q000494:pharmacology
D015220:Calcium Channels; D009124:Muscle Proteins; D009947:Organotin Compounds; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D012834:Silver; C030665:triphenyltin; D000252:Calcium-Transporting ATPases; D002118:Calcium