OPIOID PEPTIDE RECEPTOR STUDIES .4. ANTISENSE OLIGODEOXYNUCLEOTIDE TOTHE DELTA-OPIOID RECEPTOR DELINEATES OPIOID RECEPTOR SUBTYPES

Prior work in our laboratory has identified putative subtypes of delta (delta(cx-1), delta(cx-2), delta(ncx-1), delta(ncx-2)) and kappa(2) ( kappa(2a) and kappa(2b)) receptors, Previous studies showed that chron ic (three day) i.c.v. administration of antisense oligodeoxynucleotide to the cloned delta opioid receptor selectively decreased [H-3][D-Ala (2),D-Leu(5)]enkephalin binding to the delta(ncx) site, not the delta( cx-2) site. The present study extends this work by demonstrating that delta antisense DNA selectively affects the delta(ncx-2) site sparing the other putative delta receptor subtypes and kappa(2) receptor subty pes. This selectivity is not due to anatomically specific effects of d elta antisense DNA since autoradiograms show that delta binding is red uced in all regions of the brain after chronic i.c.v. administration o f delta antisense DNA. These data strongly suggest that the delta(cx-1 ), delta(cx-2), delta(ncx-1), kappa(2a), and kappa(2b) binding sites a re different proteins than the delta(ncx-2) binding site, which, based on its sensitivity to delta antisense DNA, is synonymous to the clone d delta opioid receptor, Viewed collectively, these data suggest that administration of delta antisense DNA, and by extension other receptor -selective antisense DNA, is a powerful approach to distinguishing bet ween postulated receptor subtypes.