CHARACTERIZATION OF THE ADENOSINE RECEPTOR IN MICROVASCULAR CORONARY ENDOTHELIAL-CELLS

In the present work we studied the effect of adenosine and various ade nosine analogues on cAMP level in guinea pig coronary endothelial cell s of microvascular origin. The tested adenosine agonists mediate a con centration-dependent increase in cAMP level. The rank order of potency was 5'-N-ethylcarboxamidoadenosine (NECA)> CGS 21680 > N-6 phenylisop ropyladenosine (R-PIA)> 2-chloro-N-6-cyclopentyladenosine (CCPA) which is typical for an adenosine A(2) receptor. Their respective concentra tions for half maximal stimulation of cAMP formation were 0.36 mu M, 0 .82 mu M, 4.7 mu M and 9.8 mu M. The tested agonists showed difference s in efficacy, NECA being the most efficacious. R-PIA, CCPA and adenos ine were less efficacious, suggesting partial agonism. The efficacy of adenosine was unchanged by the addition of the nucleoside transport i nhibitor S(4-nitrobenzyl)-6-thioinosine (NBTI, 10 mu M) suggesting tha t inhibition of adenylyl cyclase through P-site activation is not resp onsible for the observed low efficacy of adenosine. We could demonstra te CGS 21680 activation of adenylyl cyclase in a peripheral receptor. We therefore suggest that the endothelial adenosine receptor resembles the striatal adenosine A(2), receptor.