Abstract

It has been reported that adenosine has two 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. Therefore, the aim of this investigation was to characterize the subtype of adenosine receptor in bovine coronary arteries with the use of several adenosine analogs. The order of potency for several of these analogs was found to be: 5'-N-ethylcarboxamideadenosine greater than 5'-N-cyclopropylcarboxamideadenosine greater than L-PIA greater than N6-cyclohexyladenosine greater than 2-Cl-adenosine greater than adenosine greater than 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 found to be 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. In addition, inosine caused the dilation of both large and small coronary arteries at 1 X 10(-4)M and 1 X 10(-3)M concentrations (adenosine would cause a similar relaxation at 500-fold less concentration).(ABSTRACT TRUNCATED AT 250 WORDS)