Pol Olga, Puig Margarita M
Department of Anesthesiology, Hospital Universitario del Mar, Universidad Autónoma de Barcelona and Institut Municipal d'Investigació Mèdica, Barcelona, Spain.
Curr Top Med Chem. 2004;4(1):51-61. doi: 10.2174/1568026043451519.
Opioid receptors (OR) and their mRNA are present in the central and peripheral nervous system of mammals. In this review we examine the behavioral effects of opioids and the expression of their receptors during peripheral inflammation in two experimental models: the rat paw and the mouse intestine. Inflammation increased the antinociceptive (paw) and the inhibitory effects of opioids in the gut (transit, permeability and plasma extravasation) by interaction with OR located at peripheral sites. Based on agonist efficacy, micro > delta >> kappa-OR mediate the antinociceptive and antitransit effects of opioids during inflammation. Intestinal permeability is modulated by delta = micro >> kappa-OR, while kappa > delta >> micro-OR are involved in the inhibition of plasma extravasation. Intestinal inflammation increased the transcription of micro and delta-OR (but not kappa) genes in the gut, thus explaining the enhanced antitransit and antisecretory effects of micro and delta-OR agonists; however, the increased inhibitory effects of kappa-OR agonists on plasma extravasation could result from post-transcriptional regulation of the receptor. Similarly, the increased expression of peripheral micro-OR observed in the rat paw during inflammation, occurs at post-transcriptional levels and is related to an increased axonal transport from the dorsal root ganglia to peripheral terminals. The sites and mechanisms implicated in the increased transcription of micro and delta-OR during intestinal inflammation are under investigation.
阿片受体（OR）及其信使核糖核酸存在于哺乳动物的中枢和外周神经系统中。在本综述中，我们在两种实验模型（大鼠爪和小鼠肠道）中研究了阿片类药物的行为效应及其受体在周围炎症期间的表达。炎症通过与位于外周部位的阿片受体相互作用，增强了阿片类药物在肠道中的抗伤害感受（爪）和抑制作用（转运、通透性和血浆外渗）。基于激动剂效力，在炎症期间，微小>δ>>κ阿片受体介导阿片类药物的抗伤害感受和抗转运作用。肠道通透性由δ=微小>>κ阿片受体调节，而κ>δ>>微小阿片受体参与血浆外渗的抑制。肠道炎症增加了肠道中微小和δ阿片受体（而非κ阿片受体）基因的转录，从而解释了微小和δ阿片受体激动剂增强的抗转运和抗分泌作用；然而，κ阿片受体激动剂对血浆外渗的抑制作用增强可能是由于受体的转录后调节。同样，在炎症期间大鼠爪中观察到的外周微小阿片受体表达增加发生在转录后水平，并且与从背根神经节到外周终末的轴突运输增加有关。肠道炎症期间微小和δ阿片受体转录增加所涉及的部位和机制正在研究中。
