백서와 기니픽 대뇌 피질의 오피오이드 Kappa-2수용체 결합특성

Characteristice of Opioid Kappa-2 Receptor Binding of Bremazocine in Rat and Guinea Pig Cortex

It has been widely accepted that there are 3 types o f opioid receptors in mammalian brain, namely p, 8 and k. Recently, multiplicity of each type of opioid receptor was established owing to advance of receptor identification technology and development of more selective ligands. Even though the presence of subtype of a:-opioid receptor was reported repeatedly, selective agonist of antagonist for A：2-opioid receptor has not been found yet. In this study, the in fluences of GTPy S, a nonhydrolyzable guanine nucleotide analogue, and Na+on binding affinity and density of several known 《-agonists and antagonists for [ H ]dipem orphine(DIP) binding site in the presence of excess of DAMGO (ljjM ) and D P D P E (lfiM ) as blocking ligands for pand &ites. Competition analysis in both rat and guinea pig cortex has shown a single population of [3H ]D IP binding site with different Kd values. U 69,593(U 69) could not in hibit the [3H ]D IP binding even at lOpM concentration. By the replacement of NaCl with NMethyl- D-Glucamine(NMDG), the Ki values of D IP and Bremazocine(BRM) were not changed, and of ethylketocyclazocine(EKC) was decreased in the rat. But, in the guinea pig, the Ki values of EKC and BRM were decreased leaving the of D IP unchanged. This suggests the B RM would possess the decreased leaving that of D IP unchanged. This also suggests that B RM would possess the antagonistic property at k2 site which is dom inant type of k-opioid receptor in the rat cortex. The Ki values o f EKC were increased by the addition lOOpM of GTPy S but not by 50]jM in the rat. In guinea pig cortex, the Ki values of U 69, EKC and BRM were increased by both 50 and lOOpM of GTPy S. This results suggest that 자 opioid receptor is more sensitive to Na+ and guanine nucleotide than fc2 site, and bremazocine apparently possesses antagonistic property at fc2 site