사람 대뇌피질에서 Opioid Mu 수용체 Subtypes 의 약물결합 특성 = Ligand Binding Profile of the Subtypes of Mu-Opioid Receptors in Human Cerebral Cortex Membranes

다국어 초록 (Multilingual Abstract)

Multiplicity of opioid receptor is widely accepted, and the existence of subtypes of the three main types (μ, δ and κ) has been proposed. In present study, the existence and the ligand binding characteristics of subtypes of opioid μ-receptors were examined by the use of [^3H]D-Ala^2, D-Leu^5]enkephalinamide ([^3H]DADLE) (for μ_1-receptor, with 10 nM D Pen^2, D-Pen^5)enkephalin (DPDPE)), and [^3H][D-Ala^2,N-Me-Phe^4,Gly-ol^5]-enkephalin (DAMGO) (for μ_2-receptor, with 5 nM DADLE) in human cerebral cortex membranes.
[^3H]DADLE (1 nM), in the presence of 10 nM DPDPE to block δ-receptors, labeled single population of binding sites. Specific binding of [^3H]DADLE was displaced by opioids which display μ-agonistic activity, such as Tyr-D-Arg-Phe-Sar (TAPS), DAMGO, fentanyl, morphine and [D-Ser^2, Leu^5]enkephalyl-Thr (DSLET). The rank or of affinity was TAPS > DAMGO > morphine > fentanyl > DSLET. D-Pen-Cys-Tyr-D-Trp-OrnThr-Pen-Thr-NH_2 (CTOP), a potent and selective μ-antagonist, showed higher affinity than naloxone, a nonselective opioid antagonist. Β-Endorphin was more effective in displacement of [^3H]DADLE binding than dynorphin A (1-13).
[^3H]DAMGO (1 nM), in the presence of 5 nM DADLE to block δ-receptors, labeled single population of binding sites. Specific binding of [^3H]DAMGO to these sites was sensitively displaced by TAPS, DAMGO, fentanyl, morphine and DSLET. The rank order of affinity was different from that of μ_1-receptors; i.e. DAMGO > morphine = fentanyl = TAPS > DADLE > DSLET. Like in the case of μ^1-receptors, CTOP showed higher affinity than naloxone. Β-Endorphin was more effective in displacement of [^3H]DADLE binding than dynorphin A (1-13). Most of ligands that we used in this experiments have lower Kd values for μ_1-sites, except β-endorphin.
These results suggest that there are subtypes of opioid μ-receptors, namely μ^1 and μ^2, in human cerebral cortex, and the receptor binding profile is different from each other.

목차 (Table of Contents)

• 서론
• 실험방법
• 실험성격
• 고안
• 요약
• 참고문헌