Specific muscarinic-cholinergic desensitization in the neuroblastoma-glioma hybrid NG108-15.

The cholinergic agonist carbachol, epinephrine, and the opiate morphine all inhibit prostaglandin E1 (PGE1)-stimulated adenylate cyclase in homogenates from the neuroblastoma-glioma hybrid NG108-15. Pretreatment of the hybrid with 100 microM carbachol resulted in the rapid loss (desensitization) of the carbachol inhibition of adenylate cyclase (t1/2 less than 3 min). The desensitization of the carbachol inhibition was blocked by 0.1 microM atropine. Pretreatment with carbachol (1-24 h) did not significantly affect the inhibition of adenylate cyclase by either epinephrine or morphine, nor did it alter the PGE1-stimulated activity, that is, no supersensitization was observed. Cholate extracts of the particulate fraction from either carbachol-desensitized or of control NG108-15 were able to reconstitute adenylate cyclase activities of the coupling proteins (G/F)-deficient cyc- lymphoma cell membranes with equal efficacy. These results suggested that the coupling proteins of the adenylate cyclase were not altered by the carbachol pretreatment and that desensitization occurs at the receptor or at a receptor-associated level. However, the possibility remained that specific domains of the G/F, which interact only with muscarinic receptors, were altered.