ANALYSIS OF P-2-PURINOCEPTOR SUBTYPES ON THE SMOOTH-MUSCLE AND ENDOTHELIUM OF RABBIT CORONARY-ARTERY

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 much greater than 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 P-1- and P-2Y-purinoceptors on smooth muscle and, to a lesser extent, on endothelium and P-2X-purinoceptors, mediating transient vasoconstriction on smooth muscle alone. The presence of smooth muscle P-2Y-purinoceptors is unusual and has functional implications regarding the nature of the response of the coronary artery to ATP.