OPIOID PEPTIDE RECEPTOR STUDIES .8. ONE OF THE MOUSE-BRAIN DELTA(NCX)BINDING-SITES IS SIMILAR TO THE CLONED MOUSE OPIOID DELTA-RECEPTOR - FURTHER EVIDENCE FOR HETEROGENEITY OF DELTA-OPIOID RECEPTORS

Quantitative ligand binding studies resolved two subtypes of the delta opioid receptor, termed delta(ncx1) and delta(ncx2), in mouse brain m embranes depleted of mu receptors by pretreatment with the irreversibl e ligand, BIT. The purpose of the present study was to compare the bin ding parameters, ligand-selectivity profile and pharmacological proper ties of the cloned mouse delta receptor (MDOR) stably expressed in a c ell line to the delta(ncx) binding sites of mouse brain. [H-3][D-Ala(2 ),D-Leu(5)]enkephalin labeled a single binding site in membranes prepa red from MDOR cells under several different assay conditions including BIT-pretreatment. The MDOR had high affinity for delta agonists and a ntagonists. [H-3][D-Ala(2),D-Leu(5)]enkephalin labeled two binding sit es in mouse brain membranes depleted of mu receptors by pretreatment w ith BIT: the delta(ncx1) site (high affinity for DPDPE and deltorphin) and the delta(ncx2) site (low affinity for DPDPE and deltorphin). Som e agents were moderately selective for the delta(ncx2) site: [pCl]DPDP E (10.9-fold), JP41 (5.9-fold) and JP45 (3.8-fold). The K-i values of 12 opioids at the mouse MDOR were determined. These values were highly correlated with their values at the delta(ncx1) site but not the delt a(ncx2) site. These data suggest that the delta(ncx2) site may be dist inct from the cloned delta opioid receptor. (C) 1998 Elsevier Science Inc.