Receptor subtypes mediating adenosine-induced dilation of cerebral arterioles

The purpose of this study was to investigate the receptor subtypes that med iate the dilation of rat intracerebral arterioles elicited by adenosine. Pe netrating arterioles were isolated from the rat brain, cannulated with the use of a micropipette system, and luminally pressurized to 60 mmHg. Both ad enosine and the A(2A) receptor-selective agonist CGS-21680 induced dose-dep endent vasodilation (-logEC(50): 6.5 +/- 0.2 and 8.6 +/- 0.3, respectively) . However, adenosine, which is capable of activating both A(2A) and A(2B) r eceptors, caused a greater maximal dilation than CGS-21680. The A(2A) recep tor-selective antagonist ZM-241385 (0.1 mM) only partially inhibited the di lation induced by adenosine but almost completely blocked CGS-21680-induced dilation. Neither 8-cyclopentyl-1,3-dipropylxanthine (0.1 muM), an A(1) re ceptor-selective antagonist, nor MRS-1191 (0.1 muM), an A(3) receptor-selec tive antagonist, attenuated adenosine dose responses. Moreover, ZM-241385 h ad no effect on the dilation induced by ATP (10 muM) or acidic (pH 6.8) buf fer. We concluded that the A(2A) receptor subtype mediates adenosine-induce d dilation of intracerebral arterioles in the rat brain. Furthermore, our r esults suggest that A(2B) receptors may also participate in the dilation re sponse to adenosine.