ATP mediates coronary vasoconstriction via P2x-purinoceptors and coronary vasodilatation via P2y-purinoceptors in the isolated perfused rat heart.
The effect of ATP and its analogues on the perfusion pressure of the rat coronary vasculature and the left ventricular pressure of the isolated Langendorff perfused rat heart was examined. The response to ATP was generally biphasic, causing an increase followed by a decrease in perfusion pressure. The rank order of potency of the analogues for eliciting the vasoconstriction component was alpha,beta-methyleneATP greater than 2-methylthioATP greater than ATP, which resembles the pattern previously observed for the P2x-purinoceptor. In causing vasodilation, the rank order of antagonist potency was 2-methylthioATP greater than ATP, with alpha,beta-methyleneATP being without effect; this is a characteristic of P2y-purinoceptors. 1,3-Dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX) antagonised some of the vasodilatory effects of ATP, showing that some of the effect is due to breakdown to adenosine. Reactive blue 2, a putative P2y-purinoceptor antagonist was found to be five times more effective at antagonising the vasodilatory responses to 2-methylthioATP than to adenosine or the vasoconstriction responses to alpha,beta-methyleneATP. We suggest that ATP exerts its biphasic effects in the coronary vasculature of the rat by interacting with P2x- and P2y-purinoceptors and partly via P1-purinoceptors after breakdown to adenosine. Reactive blue 2 was more effective at antagonising responses mediated via P2y-purinoceptors than by P2x- or P1-purinoceptors.
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology*; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate