EVIDENCE SUGGESTING AN RA-TYPE ADENOSINE RECEPTOR IN BOVINE CORONARY-ARTERIES

Abstract

Adenosine has 2 extracellular membrane receptors depending upon the activation (Ra) or inhibition (Ri) of the adenylate cyclase system. At the Ra site, 5''-N-ethylcarboxamideadenosine is more potent than N6-L-phenylisopropyladenosine (L-PIA) and the reverse is true for the Ri site. The subtype of adenosine receptor in bovine coronary arteries was studied with the use of several adenosine analogs. The order of potency for several of these analogs was: 5''-N-ethylcarboxamideadenosine > 5''-N-cyclopropylcarboxamideadenosine > L-PIA > N6-cyclohexyladenosine > 2-Cl-adenosine > adenosine > D-PIA. The concentration-response curves were parallel to each other, which suggests the same receptor site. L-Adenosine, L-5''-N-ethylcarboxamideadenosine and methyl-N6-cyclohexyladenosine and 2''-5''-dideoxyadenosine (P site analog) were ineffective in relaxing the bovine coronary arteries. The difference between L- and D-PIA was less than 100-fold. This hierarchy suggested the existence of Ra subtype adenosine receptor in bovine coronary arteries. Both theophylline and 8-phenyltheophylline antagonized the relaxing effect of various analogs and shifted the concentration-response curve to the right in parallel. 8-Phenyltheophylline was severalfold more potent in its antagonistic effect than theophylline. Inosine caused the dilation of both large and small coronary arteries at 1 .times. 10-4 and 1 .times. 10-3 M concentrations (adenosine would cause a similar relaxation at 500-fold less concentration). Inosine dilated the large vessels more than small vessels. 8-Phenyltheophylline (2 .times. 10-5 M) had no effect on the inosine-induced relaxations in either large or small vessels. Adenosine deaminase rapidly reversed the adenosine-induced relaxation, whereas the reversal of inosine-induced relaxation by nucleoside phosphorylase was slower in onset. These data suggest extracellular sites for their action. Inosine may be causing its effect through some metabolic processes in addition. An Ra subtype adenosine receptor may mediate the physiological relaxation and an extracellular site may exist for the action of inosine.