Pharmacological characterization of the cloned kappa opioid receptor as a kappa_1b subtype

Substantial pharmacological evidence in vitro and in vivo has suggested the existence of subtypes ofthe kappa opioid receptor. Quantitative radioligand binding techniques resolved the presence of two high affinity binding sites for the, ligand [3H]U69,593 in mouse brain membranes, termed k¹ and, respectively. Whereas the xu site has high affinity for fedotozine and oxymorphindole and low affinity for bremazocine and a-neoendorphin, site Alb has high affinity for bremazocine and a-neoendorphin and low affinity for fedotozine and oxymorphindole. 977 and U69,593 bind equally well at both sites. To determine the relationship between these x, receptor sub-types and the recently cloned mouse x, 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, a-neoendorphin, fedotozine and oxymorphindole resolved a single class of binding sites at which these agents had binding affinities similar to that of the site present in mousebrain. These results suggest that the cloned KOR corresponds to the k, site in mouse brain defined as.