A Hormone‐independent Rise of Adenosine 3′,5′‐Monophosphate Desensitizes Coupling of β‐Adrenergic Receptors to Adenylate Cyclase in Rat Glioma C6‐Cells

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Abstract
An elevation of the intracellular c[cyclic]AMP concentration in C6 cells by cholera toxin or the cyclic nucleotide phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine causes a desensitization of the .beta.-adrenergic-receptor-dependent synthesis of cAMP. 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. The desensitization apparently is caused by an inhibition of .beta.-receptor coupling to the GTP-binding coupling protein in the adenylate cyclase complex. The loss of .beta.-receptor binding observed after incubation of cells with catecholamines is not a necessary consequence of the desensitization of receptor coupling dependent on cAMP.