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 δ (δ_cx-1, δ_cx-2, δ_ncx-1, δ_ncx-2) and κ₂ (κ_2a and κ_2b) receptors. Previous studies showed that chronic (three day) i.c.v. administration of antisense oligodeoxynucleotide to the cloned δ opioid receptor selectively decreased [³H][d-Ala²,d-Leu⁵]enkephalin binding to the δ_ncx site, not the δ_cx-2 site. The present study extends this work by demonstrating that δ antisense DNA selectively affects the δ_ncx-2 site sparing the other putative δ receptor subtypes and κ₂ receptor subtypes. This selectivity is not due to anatomically specific effects of δ antisense DNA since autoradiograms show that δ binding is reduced in all regions of the brain after chronic i.c.v. administration of δ antisense DNA. These data strongly suggest that the δ_cx-1, δ_cx-2, δ_ncx-1, κ_2a and κ_2b binding sites are different proteins than the δ_ncx-2 binding site, which, based on its sensitivity to δ antisense DNA, is synonymous to the cloned δ opioid receptor. Viewed collectively, these data suggest that administration of δ antisense DNA, and by extension other receptor-selective antisense DNA, is a powerful approach to distinguishing between postulated receptor subtypes.