It has been widely accepted hat there are 3 types of opioid receptors in mammalian brain, namely μ,δ and k. Recently, multiplicity of each type 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 k-opioid receptor was reported repeatedly, selective agonist of antagonist for k2-opioid receptor has not been found yet. In this study, the influences of GTPy S, a
nonhydrolyzable guanine nucleotide analogue, and Na+ on binding affinity and density of several known k-agonists and antagonists for [3H] dipernorphine(DIP) binding site in the presence of excess of DAMGO(lμM) and DPDPE(1μM) as blocking ligands
for μ
and δsites. Competition analysis in both rat and guinea pig cortex has shown a single population of [3H]DIP binding site with different Kd values. U69,593(U69) could not inhibit the [3H]DIP binding event at 10μM concentration. By the
replacement
of
NaCI with N-Methyl-D-Glucamine(NMDG), the Ki values of DIP and Bremazocine(BRM) were not changed, and of ethylketocyclazocine(EKC) was decreased in the rat. But, in the rat. But, in the guinea pig, the Ki values of EKC and BRM were decreased
leaving the
of DIP unchanged. This suggests the BRM would possess the decreased leaving that of DIP unchanged. This also suggests that BRM would possess the antagonistic property at k2 site which is dominant type of k-opioid receptor in the rat cortex. The
Ki
values of EKC were increased by the addition 100μM of GTPy S but not by 50μM in the rat. In guinea pig cortex, the Ki values of U69, EKC and BRM were increased by both 50 and 100μM of GTPy S.
This results suggest that k1opioid receptor is more sensitive to Na+ and guanine nucleotide than k2 site, and bremazocine apparently possesses antagonistic property at k2 site.
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