Guinea-pig tracheal epithelial cells, like other pulmonary cells in various species, have been reported to synthesize and release endothelins (ET). Their production is inducible by many agents and inhibited by ET-converting enzyme inhibitors, corticosteroids and beta agonists. Here, we studied the effect of adenosine on (1) the formation of adenosine 3', 5'-cyclic monophosphate (cAMP) and (2) concomitant effect on the basal release of ET from primary cultured tracheal epithelial cells isolated from guinea-pigs (GPTEpC). Adenosine (10(-7)-10(-3) M), the endogenous non-selective purinergic receptor agonist, induced the production of cAMP in a concentration-dependent manner (pD2=4.99+/-0.09). Concomitantly, adenosine decreased by a maximum of 39% ET-1-production over the same concentration range (with a 96% correlation). The inhibitory effect over ET-1-production was abolished by CGS15943 (10(-4) M), a non-selective A1/A2A receptor antagonist, and a xanthine amine congener (10(-4) M), a selective A1 receptor antagonist. Thus, these results suggest that adenosine attenuates the production of ET-1 from GPTEpC by stimulating the release of cAMP via the direct activation of adenosine receptors.
Copyright 1998 Academic Press.