Cyclic AMP produces desensitization of prostacyclin and adenosine A 2 receptors in hybrid cell lines but does not affect G s function

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Prostacyclin and adenosine A 2 receptors stimulate adenylate cyclase activity in the related somatic hybrid cell lines NG108-15 and NCB20. The role of cAMP in the desensitization of these receptors has been examined. Pretreatment for 17 h with forskolin or 8-bromo-cAMP had the same effect in both cell lines. There was no change in the response to sodium fluoride or forskolin, suggesting that the function of G s and adenylate cyclase were unaffected by increased levels of cAMP. Receptor responses were affected however; the maximum response to N-ethylcarboxamidoadenosine (an A 2 receptor agonist) was reduced by 30–40%, there was a small but consistent shift to the right of the dose-response curve for iloprost (a stable analogue of prostacyclin) and [ 3H]iloprost binding studies revealed a loss of prostacyclin receptors. However, the loss of receptor responsiveness was much smaller than that which occurs following pretreatment with prostacyclin or adenosine A 2 receptor agonists (Keen et al. (1989) Biochem. Pharmacol. 38, 3827–3833; Kelly et al. (1990) Br. J. Pharmacol. 99, 309–316) suggesting that cAMP may not play a major role in agonist mediated desensitization.