Adenosine relaxes the aorta by interacting with an A2 receptor and an intracellular site.

The purpose of this study was to determine whether the adenosine receptor that mediates relaxation of the noradrenaline-contracted guinea-pig aorta is of the A1 or A2 subtype. 5'-N-ethylcarboxamide adenosine (NECA) and 5'-N-cyclopropylcarboxamide adenosine (NCPCA) were about 100 times more potent as relaxants of the aorta than L-N6-phenylisopropyladenosine (L-PIA) and N6-cyclohexyladenosine. L-PIA was 3 times more potent than D-PIA. These relaxations were not altered by the purine transport inhibitor dipyridamole, but were attenuated by the cell surface adenosine receptor antagonist 8-phenyltheophylline. Adenosine and 2-chloroadenosine differed from NECA and NCPCA since they evoked greater maximal relaxations and their submaximal responses were less sensitive to blockade by 8-phenyltheophylline. These differences were abolished by dipyridamole which indicates that they were due to an intracellular action of adenosine and 2-chloroadenosine. The intracellular 'P-site' agonist, 9-beta-D-xylofuranosyladenine evoked small relaxations that were attenuated by dipyridamole but were unaffected by 8-phenyltheophylline. These results indicate that adenosine can relax the aorta via interactions with a cell surface A2 receptor and with an intracellular site.