Analysis of P2-purinoceptor subtypes on the smooth muscle and endothelium of rabbit coronary artery

Abstract

We studied purinoceptor subtypes mediating constriction and dilatation in isolated rabbit coronary arteries with and without endothelium by comparing the effects of adenosine, ATP and the ATP analogues, alpha, beta-methylene ATP and 2-methylthio ATP. For contraction, the rank order of agonist potency was alpha, beta-methylene ATP > 2-methylthio ATP >> ATP; adenosine did not produce contraction. Removal of the endothelium did not affect these responses, but they were abolished by previous desensitisation with alpha, beta-methylene ATP. For relaxation, adenosine, ATP, and 2-methylthio ATP were equipotent, but alpha, beta-methylene ATP had no vasodilator effect and caused further contraction of the preparations. A transient contraction often preceded the relaxations to ATP at higher concentrations. The dilator responses to adenosine, ATP, and 2-methylthio ATP were significantly reduced but not abolished in preparations denuded of endothelium; previous desensitisation with alpha, beta-methylene ATP had no effect on the relaxant responses but abolished the initial transient contractions to ATP and 2-methylthio ATP. These results indicate the presence of vasodilator P1- and P2Y-purinoceptors on smooth muscle and, to a lesser extent, on endothelium and P2X-purinoceptors, mediating transient vasoconstriction on smooth muscle alone. The presence of smooth muscle P2Y-purinoceptors is unusual and has functional implications regarding the nature of the response of the coronary artery to ATP.