Alteration in cardiac sarcolemmal ATP receptors by oxyradicals.
We previously demonstrated that cardiac sarcolemmal membranes bind [35S]ATP gamma S at both low and high affinity binding sites. In this study we examined the effects of some P2-purinoceptor antagonists as well as of two oxidants (H2O2 and HOCl) on the high affinity ATP-binding sites under in vitro conditions. It was found that putative P2-purinoceptor antagonists such as Cibacron blue, suramin, and 4,4'-diisothiocyanatostilbene 2-2 acid markedly inhibited specific ATP-binding with sarcolemmal membrane. H2O2 produced a biphasic effect (first increase and then decrease) on the specific ATP-binding with cardiac sarcolemma in a time- and concentration-dependent manner; these effects were prevented by catalase. On the other hand, HOCl markedly inhibited ATP-binding; this inhibition was prevented by l-methionine. These results suggest that the high affinity ATP-binding sites in cardiac sarcolemma may represent the P2-purinoceptors, which are susceptible to modification by oxidative stress under pathophysiological conditions including myocardial ischemia-reperfusion injury.
Musat
S
S
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Dhalla
N S
NS
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism*
D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate