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백서와 기니픽의 대뇌피질에서 Opioid Kappa 수용체의 특성에 관한 연구
김기원(Kee-Won Kim),노혜원(Hye-Won Rho),김형일(Hyoung-Il Kim),은재순(Jae-Soon Eun),소수미(Soo-Mi Soh),조규박(Kyu-Park Cho) 대한약리학회 1994 대한약리학잡지 Vol.30 No.2
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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사람 대뇌피질에서 Kappa Opioid 수용체의 이질성
소수미,한낙천,장전,은재순,김기원 의과학연구소 1996 全北醫大論文集 Vol.20 No.1
Experimental data have shown that there are considerable species differences in the distribution of opioid receptor types in mammalian brain. We have evaluated the properties of non-μ non-δ binding of [^3H]-diprenorphine([^3H]DIP), a nonselective opioid antagonist, in human cortex membranes. Bindings to μ and δ site were inhibited by the use of an excess of competing selective agonists, DAMGO(1μM) and DPDPE(1 μM), for these sites. Dynorphine-A(1-13), U-69, 593 and U-50, 488H, selective k_1 agonists, (-)ethyketocyclazocine and nor-binaltorphimine, k_1 and k_2 opioid ligands, inhibited the [^3H] DIP binding to human cortex membranes with high affinities. In the presence of cold ligands, I μM each of DAMGO, DPDPE and U-69, 593, that block μ-, δ-, and k_1 sites, poioid binding still remained. Specific binding of[^3H]DIP to this stie was not influenced by U-50, 488H or β-endorphin even in micromolar dose range, but inhibited y DIP, bremazocine, (-)eyhylketocylazocine and nor-binaltorphimine. The concentration-inhibition curves of these ligands in the presence of DAMGO and DPDPE were displaced further to right by the addition of U-69, 593. These data suggest that there are at least 2 kinds of k-opioid binding sites(k_1 and k_2) in human cortex.
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