OPIOID PEPTIDE RECEPTOR STUDIES .4. ANTISENSE OLIGODEOXYNUCLEOTIDE TO THE 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 chronic (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 subtypes. This selectivity is not due to anatomically specific effects of delta antisense DNA since autoradiograms show that delta binding is reduced in all regions of the brain after chronic i.c.v. administration of 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 are different proteins than the delta(ncx-2) binding site, which, based on its sensitivity to delta antisense DNA, is synonymous to the cloned 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 between postulated receptor subtypes.