DIFFERENT P2-PURINERGIC RECEPTOR SUBTYPES OF ENDOTHELIUM AND SMOOTH-MUSCLE IN CANINE BLOOD-VESSELS

Publisher Website
Google Scholar
Abstract
P2-Purinergic agonists can induce direct contractions in saphenous veins and endothelium-dependent relaxations in coronary arteries of the dog. For contractions, the rank order of agonist potency was .alpha.,.beta.-methylene-ATP .mchgt. ATP > ADP. For endothelium-dependent relaxation, the order was 2-methylthio-ATP > ADP > ATP .mchgt. .alpha.,.beta.-methylene-ATP (the latter causing no relaxation) suggesting two different subtypes of the P2-purinoceptors in these tissues. .alpha.,.beta.-Methylene-ATP could be used like an antagonist in the saphenous vein because it desensitizes receptors; exposure to it prevented contractions to ADP or ATP, but did not inhibit relaxations to them in the coronary artery. Reactive blue 2, from 2 .times. 10-6 to 2 .times. 10-5 M, behaved as a competitive antagonist of relaxations of the coronary artery induced by ADP and 2-methylthio-ATP; it did not inhibit contraction of the saphenous vein by .alpha.,.beta.-methylene-ATP. It antagonized slightly the endotehelium-dependent relaxation of the coronary artery to acetylcholine, but not that to the calcium ionophore A23187. In contrast, methylene blue, a functional antagonist of endothelium-dependent relaxations, caused noncompetitive antagonism of relaxation to the same agonists. Thus, different subtypes of P2-purinoceptors on canine vascular smooth muscle and endothelium can be distinguished on the basis not only of the potencies of a series of agonists, but by two antagonists which discriminate between them.