Selective labeling of κ2 opioid receptors in rat brain by [I]IOXY: Interaction of opioid peptides and other drugs with multiple κ2a binding sites |
| |
Authors: | Q. Ni Heng Xu John S. Partilla Brian R. De Costa Kenner C. Rice Richard B. Rothman |
| |
Affiliation: | * Clinical Psychopharmacology Section, Addiction Research Center, National Institute on Drug Abuse, NIH, PO Box 5180, Baltimore, MD 21224, USA † Laboratory of Medicinal Chemistry, NIDDK, NIH, Bethesda, MD 20892, USA |
| |
Abstract: | Recent studies from our laboratory resolved two subtypes of the κ2 binding site, termed κ2a and κ2b, using guinea pig, rat, and human brain membranes depleted of μ and δ receptors by pretreatment with the site-directed acylating agents BIT (μ-selective) and FIT (δ-selective). 6β-Iodo-3,14-dihydroxy-17-cyclopropylmethyl-4,5-epoxymorphinan (IOXY), an opioid antagonist that has high affinity for κ2 sites, was radioiodinated to maximum specific activity (2200 Ci/mmol) and purified by high pressure liquid chromotography and used to characterize multiple κ2 binding sites. The results indicated that [125I]IOXY, like [3H]bremazocine, selectively labels κ2 binding sites in rat brain membranes pretreated with BIT and FIT. Using 100 nM [-Ala2-MePhe4,Gly-ol5]enkephalin to block [125I]IOXY binding to the κ2b site, two subtypes of the κ2a binding site were resolved, both in the absence and presence of 50 μM 5′-guanylyimidodiphosphate. Viewed collectively, these results provide further evidence for heterogeneity of the κ opioid receptor, which may provide new targets for drug design, synthesis, and therapeutics. |
| |
Keywords: | Opioid receptors Kappa opioid receptors Dynorphin Endorphins IOXY |
本文献已被 ScienceDirect 等数据库收录! |
|