Desensitization of β-adrenergic receptor-coupled adenylate cyclase activity. Differences following exposure of cells to two full agonists

The effects on the β-adrenergic receptors of intact L6 muscle cells of exposure to agonists were investigated. Treatment of cells with isoproterenol decreased GTP-, isoproterenol-, and zinterol-stimulated adenylate cyclase activities, whereas exposure of cells to zinterol decreased only isoproterenol- and zinterol-stimulated activities. Although the effects of these two full agonists on GTP-stimulated adenylate cyclase activity were different, the time courses for development and reversal of the effects were similar. The decrease in agonist-stimulated adenylate cyclase activity observed in membranes prepared from cells previously exposed to isoproterenol or zinterol was due to both an increase in the concentration of agonist required for half-maximal activation and a decrease in the maximum level of activation. No effects on fluoride- or manganese-stimulated activities were observed following exposure of cells to either agonist. Decreases in GTP-stimulated adenylate cyclase activity were also observed following exposure of cells to epinephrine, Cc-25, fenoterol, norepinephrine, terbutaline, or metaproterenol, but not following incubation of cells with dobutamine or salmefamol. The results suggest that full agonists interacting with the same receptor can induce different changes in the components of the adenylate cyclase system. Desensitization following exposure to zinterol may result from modification of the receptor, whereas that following exposure to isoproterenol may be due to alterations in both the guanine nucleotide-binding protein and the receptor.