氢化可的松可加强京都酚及其类似物的镇痛效应

THE PERMISSIVE ACTION OF GLUCOCORTICOID ON THE ANALGESIC EFFECT OF KYOTORPHIN AND ITS ANALOGUE

利用氢化可的松同京都酚(kyotorphin,KTP)或其类似物(riKTP)结合成的缀合物,观察糖皮质激素的允许作用,并对KTP(二肽)的镇痛的机理作进一步探讨。实验表明:icv KTP和riKTP有明显镇痛效应,并存在量效关系;氢化可的松无明显的镇痛效应;无论是缀合物还是氯化可的松与二肽的混合物,其镇痛作用均比相应剂量的二肽明显增强,而缀合物同混合物相比,镇痛作用无显著差异;sc纳洛酮(10mg/kg)不能阻断KTP或riKTP的镇痛效应。上述结果提示:糖皮质激素对二肽镇痛存在允许作用。这种作用可能是通过膜受体的快速效应实现的;二肽引起的镇痛可能与阿片受体无关,但不能排除有其它递质的释放参与镇痛。

Kyotorphin (KTP) is an endogenous analgesic dipeptide which does not act on opiate receptors but may induce the release of endogenous opioid met-enkephalin. In order to investigate whether or not glucocorticoids have 'permissive action' on KTP, hydrocortisone has been used to examine its action on the analgesic activities of KTP and its retro-isomer (riKTP) by employing thermal irradiation-tail flick method after intracerebroventricular injection.KTP and riKTP showed dose-dependent analgesic activity. Dose of KTP in the range of 6～24 mmol/L were effective, while the dose of riKTP at 6 mmol/L was shown to be ineffective. The analgesia of KTP was higher than that of riKTP. Hydrocortisone alone showed no significant analgesic effect. Linkers by connecting hydrocortisone with KTP or riKTP showed significantly higher analgesic effect compared with the corresponding dipeptides, not only in the duration of analgesia but also in potency. Solutions containing hydrocortisone and any one of the dipeptides exhibited the same effect as the linker. Pretreatment with sc naloxone (10 mg/kg) 15 min before icy of KTP or riKTP (24 mmol/L) could not block the analgesia.These findings implicate that: (1) Glucocorticoids have a permissive action on the analgesia of KTP and its retro-isomer. The glucocortieoids may exert its effects by acting on receptors in the membrane, and thus cause fast membrane effect. (2) KTP may also induce release of substances other than met-enkephalin to participate in the analgesia.