In this study, we tested the influences of several κ opioid ligands on the [<sup>3</sup>H]diprenorphine binding in rat and guinea pig cortex membrane preparations. Using paradigm to block μ and δ opioid receptors with DAMGO(1μM) and DPDPE(1μM), [<sup>3</sup>H]diprenorphine labeled κ sites. Competition analysis in both rat and guinea pig cortex has shown a single population of [<sup>3</sup>H]diprenorphine binding site with different Kd values, respectively. There is a significant difference in Ki values of (-) WIN44441 and (+)WIN44441 in both rat and guinea pig cortex. Bremazocine, (-)ethylketocyclazocine, (-)cyclazocine, nor-binaltorphimine effectively inhibited the [<sup>3</sup>H]diprenorphine binding with different Ki values in rat and guinea pig cortex. U-69,593, U-50,488H and dynorphine-A (1-8) did not inhibit the [<sup>3</sup>H]diprenorphine binding in rat but in guinea pig cortex. Nor-binaltorphimine was a ligand discriminate the κ<sub>1</sub>, and κ<sub>2</sub> receptor most effectively. We, also, examined the influence of Na ion and GTPγS, a nonhydrolyzable guanine nucleotide analog, on the inhibition of [<sup>3</sup>H]diprenorphine binding by diprenorphine, (-)ethyl-ketocyclazocine, U-69,593 and bremazocine. By the replacement of NaCl with N-methy-D-glucamine or addition of GTPγS, Ki values of diprenorpnine were not changed and that of ethylketocyclazocine were changed significantly in both rat and guinea pig cortex. The Ki value of bremazocine was decreased by removal of Na ion, and increased by GTPγS, however, was not changed by any one of either. These results suggest that there are 2 kinds of subtypes of κ opioid receptor, κ<sub>1</sub>, and κ<sub>2</sub>, showing different Ki values for various κ opioid ligands, also, bremazocine possess the antagonistic property at κ<sub>2</sub> site which is dominant subtype of K receptor in rat cortex.
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