Kest B, Orlowski M, Bodnar R J
Department of Psychology, Queens College, CUNY, Flushing 11367.
Physiol Behav. 1991 Oct;50(4):843-5. doi: 10.1016/0031-9384(91)90027-l.
The duration of action and potency of endogenous opioid peptides are limited by proteolytic enzymes such as endopeptidases 24.11 and 24.15. Whereas endopeptidase 24.11 cleaves enkephalin pentapeptides, endopeptidase 24.15 degrades longer-chained opioids including dynorphin A1-8 and met-enkephalin-Arg6-Gly7-Leu8 (MERGL). Inhibitors of endopeptidase 24.11 and 24.15 both increase basal nociceptive thresholds and respective forms of opioid antinociception. Acute exposure to certain environmental stressors can produce antinociception which is opioid mediated; inhibitors of endopeptidase 24.11 potentiate this effect. The present study evaluated whether central administration of a selective inhibitor of endopeptidase 24.15, N-[1-(RS)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB) increased antinociception following intermittent cold-water swims (ICWS) in rats. cFP-AAF-pAB (0.25-25 nmol, ICV) dose-dependently increased ICWS antinociception on the tail-flick and jump tests without affecting basal nociceptive thresholds. The opioid mediation of ICWS antinociception was confirmed by significant reductions in this response following naloxone. These data indicate that longer-chained endogenous opioid peptides participate in the antinociception induced by ICWS.
内源性阿片肽的作用持续时间和效力受到诸如内肽酶24.11和24.15等蛋白水解酶的限制。内肽酶24.11可切割脑啡肽五肽，而内肽酶24.15则降解包括强啡肽A1 - 8和甲硫脑啡肽 - Arg6 - Gly7 - Leu8（MERGL）在内的长链阿片类物质。内肽酶24.11和24.15的抑制剂均可提高基础痛觉阈值以及各自形式的阿片类镇痛作用。急性暴露于某些环境应激源可产生由阿片类介导的镇痛作用；内肽酶24.11的抑制剂可增强这种效应。本研究评估了向大鼠脑室内注射内肽酶24.15的选择性抑制剂N - [1 -（RS） - 羧基 - 3 - 苯丙基] - Ala - Ala - Phe - 对氨基苯甲酸（cFP - AAF - pAB）是否会在间歇性冷水游泳（ICWS）后增强镇痛作用。cFP - AAF - pAB（0.25 - 25 nmol，脑室内注射）在甩尾和跳跃试验中剂量依赖性地增强了ICWS镇痛作用，且不影响基础痛觉阈值。纳洛酮处理后该反应显著降低，证实了ICWS镇痛作用是由阿片类介导的。这些数据表明长链内源性阿片肽参与了ICWS诱导的镇痛作用。
