Agonist-induced state of the delta-opioid receptor that discriminates between opioid peptides and opiate alkaloids

M Von Zastrow, DE Keith and CJ Evans

Department of Psychiatry, Stanford University Medical Center, California 94305.

We report a novel agonist-induced change in delta-opioid receptor binding properties in NG108-15 cells. Pretreatment of these cells with opioid agonists substantially diminishes the binding of peptide agonists and a peptide antagonist to opioid receptors in intact cells or membrane preparations. However, similar agonist-induced changes in the binding of opiate alkaloid agonists and antagonists were not detected. The change in opioid peptide binding occurs rapidly at 37 degrees (t1/2 approximately 10 min) but is not induced by agonist treatment at 4 degrees. Because of its lability at 37 degrees, the binding change is only detected when equilibrium binding assays are performed at 4 degrees. Both alkaloid and peptide agonists induce the binding change in a dose-dependent manner, with an ED50 for etorphine of approximately 10 nM. The induction of the binding change is completely blocked by the opiate antagonist naloxone. Stimulation of muscarinic receptors (which, like opioid receptors, inhibit adenylate cyclase in these cells) does not induce or block the binding change. These data reveal the operation of a homologous regulation mechanism that rapidly diminishes the interaction of delta-subtype opioid receptors with peptide ligands but does not detectably change the interaction of receptors with alkaloid ligands.

Volume 44, Issue 1, pp. 166-172, 07/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics

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