McHardy Smith - Modification of receptor-mediated inhibition of adenylate cyclase in NG108-15 neuroblastoma X glioma cells by n-ethylmaleimide.

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      Smith, M. M., Harden, T. K. 228 425-33-

      Abstract: Previous studies with membranes from   rat heart (Mol. Pharmacol. 21: 570-580, 1982) and human platelets   (J. Biol. Chem. 257: 2829-2833, 1982) have suggested that   inhibition of adenylate cyclase by occupation of hormone   receptors is blocked by pretreatment of membranes with relatively   low concentrations of N-ethylmaleimide (NEM). Using membranes   derived from NG108-15 neuroblastoma X glioma cells as a model   system, we have examined the effect of NEM on the interaction of   three inhibitory receptors with adenylate cyclase. Pretreatment   of membranes with 100 to 216 microM NEM resulted in a loss of the   capacity of agonists to inhibit adenylate cyclase through   muscarinic cholinergic and opiate receptors and a loss of   GTP-sensitive high-affinity binding of agonists to both of these   receptors. Under the same conditions, stimulation of adenylate   cyclase by prostaglandin E1 was unchanged. In contrast to the   total loss of capacity to inhibit adenylate cyclase by muscarinic   and opiate receptor activation, the inhibition of adenylate   cyclase by activation of alpha-2 adrenergic receptors was only   partially blocked by maximally effective concentrations of NEM.   Similarly, GTP-sensitive high-affinity binding of epinephrine to   alpha-2 receptors still occurred in NEM (316 microM)-treated   membranes. Whereas only a decrease in the efficacy of muscarinic   and opiate receptor agonists for inhibition of adenylate cyclase   occurred as a result of NEM treatment, pretreatment of membranes   with 316 microM NEM resulted in a 30-fold decrease in the potency   of epinephrine for inhibition of adenylate cyclase.(ABSTRACT   TRUNCATED AT 250 WORDS)

      Address (URL): http://www.ncbi.nlm.nih.gov/pubmed/6319678