A hormone-independent rise of adenosine 3',5'-monophosphate desensitizes coupling of beta-adrenergic receptors to adenylate cyclase in rat glioma C6-cells.

An elevation of the intracellular cAMP concentration in C6 cells by cholera toxin or the cyclic nucleotide phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine causes a densitization of the beta-adrenergic-receptor-dependent synthesis of adenosine 3',5'-monophosphate. The specific binding of [3H]dihydroalprenolol to the beta-adrenergic receptors and the activation of the adenylate cyclase in vitro by fluoride anions and guanyl imidotriphosphate remain unchanged. It is likely that the desensitization is caused by an inhibition of beta-receptor coupling to the GTP-binding coupling protein in the adenylate cyclase complex. Furthermore, these experiments provide evidence that the loss of beta-receptor binding observed after incubation of cells with catecholamines is not a necessary consequence of the densensitization of receptor coupling dependent on adenosine 3',5'-monophosphate.