Triorganotin inhibition of rat cardiac adenosine triphosphatases and catecholamine binding.
Triorganotins have been reported to affect heme metabolism as well as the cardiovascular system. Our recent studies indicated that these organotins inhibit cardiac sarcoplasmic reticulum Ca(2+)-transport and cAMP-stimulated phosphorylation of specific proteins involved in Ca2+ transport, suggesting their interference with cardiac adrenergic function. The present study determines the effect of three organotins--tributyltin bromide (TBT), triethyltin bromide (TET) and trimethyltin chloride (TMT)--on rat cardiac ATPases and catecholamine binding, since these phenomena are involved in cardiac function. Cardiac membrane fraction was prepared from heart ventricles of male Sprague-Dawley rats. All three organotins inhibited cardiac Na+,K(+)-ATPase, [3H]ouabain binding, K(+)-activated p-nitrophenyl phosphatase (K(+)-PNPPase) and oligomycin-sensitive (OS) and oligomycin-insensitive (OI) Mg(2+)-ATPase in a concentration-dependent manner. K(+)-PNPPase was less sensitive to these triorganotins when compared to Na+K(+)-ATPase, suggesting that triorganotins affect the Na(+)-pump activity by acting on the Na(+)-dependent phosphorylation process. OS Mg(2+)-ATPase was more sensitive to these organotins when compared to OI Mg(2+)-ATPase, confirming their potent effect on the enzymes of oxidative phosphorylation. The order of potency is TBT greater than TET greater than TMT. TET and TMT, but not TBT, inhibited [3H]norepinephrine and [3H]dopamine binding to cardiac membranes in a concentration-dependent manner, the effect being more with TET. These results suggest that triorganotins inhibit sodium pump activity as well as ATP synthesis. Since Na+,K(+)-ATPase is involved in the active transport of catecholamines, triorganotins not only inhibited the catecholamine transport but also to some extent affected catecholamine binding, thus interfering with cardiac function.
Cameron
J A
JA
Department of Biology, Jackson State University, MS 39217.
Kodavanti
P R
PR
Pentyala
S N
SN
Desaiah
D
D
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014267:Triethyltin Compounds / Q000633:toxicity*; D014298:Trimethyltin Compounds / Q000633:toxicity*
D002395:Catecholamines; D014220:Trialkyltin Compounds; D014267:Triethyltin Compounds; D014298:Trimethyltin Compounds; C046488:trimethyltin; C011559:tributyltin; C031575:triethyltin; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase