Inhibition of Ca2+ transport associated with cAMP-dependent protein phosphorylation in rat cardiac sarcoplasmic reticulum by triorganotins.
Organotin compounds have been shown to interfere with cardiovascular system. We have studied the in vitro and in vivo effects of tributyltin bromide (TBT), triethyltin bromide (TET) and trimethyltin chloride (TMT) on the cardiac SR Ca2+ pump, as well as on protein phosphorylation of SR proteins, in order to understand the relative potency of these tin compounds. All the three tin compounds inhibited cardiac SR 45Ca uptake and Ca(2+)-ATPase in vitro in a concentration-dependent manner. The order of potency for Ca(2+)-ATPase as determined by IC50, is TBT (2 microM) greater than TET (63 microM) greater than TMT (280 microM). For 45Ca uptake, it followed the same order i.e., TBT (0.35 microM) greater than TET (10 microM) greater than TMT (440 microM). In agreement with the in vitro results, both SR Ca(2+)-ATPase and 45Ca uptake were significantly inhibited in rats treated with these tin compounds, indicating that these tin compounds inhibit cardiac SR Ca2+ transport. cAMP significantly elevated (70-80%) the 32P-binding to SR proteins in vitro in the absence of any organotin. In the presence of organotins, cAMP-stimulated 32P-binding to proteins was significantly reduced, but the decrease was concentration dependent only at lower concentrations. The order of potency is TBT greater than TET greater than TMT. In agreement with in vitro studies, cAMP-dependent 32P bound to proteins was significantly reduced in rats treated with TBT, TET and TMT. SDS-polyacrylamide gel electrophoresis of the cardiac SR revealed at least 30 Coomassie blue stainable bands ranging from 9 to 120 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)
Kodavanti
P R
PR
Department of Neurology, University of Mississippi Medical Center, Jackson 39216.
Cameron
J A
JA
Yallapragada
P R
PR
Vig
P J
PJ
Desaiah
D
D
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics*; D002132:Calcium Radioisotopes; D000242:Cyclic AMP / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009947:Organotin Compounds / Q000633:toxicity*; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
D002132:Calcium Radioisotopes; D009124:Muscle Proteins; D009947:Organotin Compounds; D000242:Cyclic AMP; D002118:Calcium