Douglas A J, Bicknell R J, Russell J A
Department of Physiology, University Medical School, Edinburgh, Scotland, United Kingdom.
Adv Exp Med Biol. 1995;395:381-94.
Oxytocin is secreted during parturition to stimulate myometrial contractions and birth. Prior to the start of labour, oxytocin neurones undergo changes to prepare for optimal secretion during labour. Thus, during late pregnancy oxytocin secretion is limited by endogenous opioid inhibition. This does not appear to act at the oxytocin nerve terminals in the neural lobe since they in fact become desensitised to opioid inhibition, responding less to either the general opioid antagonist, naloxone, or to the specific kappa-opioid agonist U50,488, and kappa-receptor binding decreases. However, removal of opioid inhibition on oxytocin neurones by naloxone activates oxytocin cell bodies and there is an increase in the number of cells expressing Fos protein in the supraoptic nucleus. This action is mediated via mu- and not kappa-opioid receptors since norBinaltorphimine (kappa-antagonist) is ineffective. Endogenous opioids are likely to act pre-synaptically on inputs to oxytocin neurones, especially those from the brainstem since naloxone potentiates the firing rate response of oxytocin neurones to intravenous cholecystokinin administration which acts via noradrenergic neurones. The endogenous opioid, beta-endorphin may be responsible for inhibition of oxytocin neurones as both the peptide content and its precursor proopiomelanocortin mRNA content increase in the arcuate nucleus during pregnancy, whereas expression of the co-localized opioids, prodynorphin or proenkephalin A, in magnocellular neurones does not alter.
催产素在分娩过程中分泌，以刺激子宫肌层收缩并引发分娩。在分娩开始前，催产素神经元会发生变化，为分娩期间的最佳分泌做准备。因此，在妊娠晚期，催产素的分泌受到内源性阿片类物质抑制的限制。这种抑制似乎并非作用于神经垂体中的催产素神经末梢，因为实际上这些末梢对阿片类物质抑制变得不敏感，对一般阿片类拮抗剂纳洛酮或特异性κ-阿片激动剂U50,488的反应减弱，且κ-受体结合减少。然而，用纳洛酮去除对催产素神经元的阿片类物质抑制会激活催产素细胞体，并且视上核中表达Fos蛋白细胞的数量会增加。这种作用是通过μ-而非κ-阿片受体介导的，因为 norBinaltorphimine（κ-拮抗剂）无效。内源性阿片类物质可能在突触前作用于催产素神经元的输入，尤其是来自脑干的输入，因为纳洛酮增强了催产素神经元对静脉注射胆囊收缩素给药的放电频率反应，胆囊收缩素通过去甲肾上腺素能神经元起作用。内源性阿片类物质β-内啡肽可能是抑制催产素神经元的原因，因为在怀孕期间，弓状核中的肽含量及其前体阿黑皮素原mRNA含量均增加，而大细胞神经元中共定位的阿片类物质强啡肽原或脑啡肽原A的表达并未改变。
