Adenosine‐induced dilatation of the rabbit hepatic arterial bed is mediated by A2‐purinoceptors

Abstract

This study was carried out in order to identify the receptor responsible for adenosine‐induced dilatation of the hepatic arterial vascular bed. Livers of 10 New Zealand White rabbits were perfused in vitro with Krebs‐Bülbring buffer via the hepatic artery and the portal vein at constant flows of 26 and 77 ml min−1 100 g−1 liver respectively. The tone of the preparation was raised by the presence of noradrenaline in the perfusate (concentration: 10−5 m). Dose‐response curves for adenosine and its analogues 5′‐N‐ethyl‐carboxamido‐adenosine (NECA), the 2‐substituted NECA analogue CGS 21680C, and R‐ and S‐N6‐phenyl‐isopropyl‐adenosine (R‐ and S‐PIA) were obtained after their injection into the hepatic arterial supply. The order of vasodilator potency of these agents was: NECA > CGS 21680C > adenosine > R‐PIA > S‐PIA. Their potency, expressed relative to that of adenosine, was in the approximate ratio 10:3:1:0.3:0.1, consistent with that resulting from activation of P1‐purinoceptors of the A2 sub‐type (which mediate vasodilatation due to adenosine). The P1‐purinoceptor antagonist 8‐phenyltheophylline (10−5 m) caused significant attenuation of the vasodilatation to adenosine and analogues. It is concluded that adenosine‐induced dilatation of the hepatic arterial vascular bed is mediated by P1‐purinoceptors of the A2 sub‐type. 1991 British Pharmacological Society