Pharmacological characterization of the cloned kappa opioid ... : NeuroReport (original) (raw)

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Pharmacological characterization of the cloned kappa opioid receptor as a kappa1b subtype

Lai, Josephine; Ma, Shou-wu; Zhu, Rong-Huan; Rothman, Richard B.; Lentes, Klaus-Ulrich; Porreca, Frank

Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, AZ 85724; NIDA Addiction Research Center, Baltimore, MD 21224, USA; Max-Planck Institute for Biophysical Chemistry, Gottingen, Germany

Abstract

SUBSTANTIAL pharmacological evidence in vitro and in vivo has suggested the existence of subtypes of the kappa opioid receptor. Quantitative radioligand binding techniques resolved the presence of two high affinity binding sites for the _k_1 ligand [3H]U69,593 in mouse brain membranes, termed _k_1a and _k_1b, respectively. Whereas the _k_1a site has high affinity for fedotozine and oxymorphindole and low affinity for bremazocine and α-neoendorphin, site _k_1b has high affinity for bremazocine and α-neoendorphin and low affinity for fedotozine and oxymorphindole. CI-977 and 1169,593 bind equally well at both sites. To determine the relationship between these _k_1 receptor subtypes and the recently cloned mouse _k_1 receptor (KOR), we examined [3H]U69,593 binding to the KOR in stably transfected cells (KORCHN-8). Competition of [3H]U69,593 binding to the KOR by bremazocine, α-neoendorphin, fedotozine and oxymorphindole resolved a single class of binding sites at which these agents had binding affinities similar to that of the _k_1b site present in mouse brain. These results suggest that the cloned KOR corresponds to the _k_1 site in mouse brain defined as _k_1b.

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