Russell J A, Leng G, Bicknell R J
Department of Physiology, University Medical School, Edinburg, UK.
Exp Physiol. 1995 May;80(3):307-40. doi: 10.1113/expphysiol.1995.sp003850.
At the neurosecretory terminals in the neural lobe, oxytocin secretion is restrained by co-secreted endogenous opioids, which act via kappa-receptors. The co-secreted opioids include products of pro-dynorphin (released by both vasopressin and oxytocin terminals) and proenkephalin (released by oxytocin terminals). In morphine-tolerant rats this opioid mechanism is more effective, but in late pregnancy it is less effective. Opioids also act directly on oxytocin cell bodies, via separate mu- and kappa-receptors, inhibiting excitation by all stimuli tested, and also exert presynaptic and more distal actions on afferent systems. During chronic morphine exposure, tolerance and dependence develop in oxytocin neurones; the former involves reduction in mu-opioid receptor density, while the latter may involve compensatory upregulation of mechanisms regulating Ca2+ influx. In mid-pregnancy, the effectiveness of opioid mechanisms in the neural lobe increases, assisting the accumulation of oxytocin stores in advance of parturition, but by the end of pregnancy the effectiveness of these mechanisms is reduced. At this time, a separate endogenous opioid system, acting via mu-receptors, actively restrains the electrical activity of oxytocin neurones. Release of this endogenous opioid inhibition may contribute to the increase in activity during parturition analogous to that occurring during morphine withdrawal excitation. Central opioid mechanisms retain the ability to control oxytocin neurones during parturition, and can interrupt established parturition by inhibiting oxytocin neurone firing rate in disadvantageous environmental circumstances.
在神经垂体的神经分泌终末，催产素的分泌受到共同分泌的内源性阿片肽的抑制，这些阿片肽通过κ受体发挥作用。共同分泌的阿片肽包括前强啡肽的产物（由加压素和催产素终末释放）和前脑啡肽的产物（由催产素终末释放）。在吗啡耐受的大鼠中，这种阿片肽机制更有效，但在妊娠后期则效果较差。阿片肽还通过单独的μ和κ受体直接作用于催产素细胞体，抑制所有测试刺激引起的兴奋，并且还对传入系统发挥突触前和更远端的作用。在慢性吗啡暴露期间，催产素神经元会产生耐受性和依赖性；前者涉及μ阿片受体密度的降低，而后者可能涉及调节Ca2+内流的机制的代偿性上调。在妊娠中期，神经垂体中阿片肽机制的有效性增加，有助于在分娩前积累催产素储备，但到妊娠末期，这些机制的有效性降低。此时，一个单独的内源性阿片肽系统通过μ受体发挥作用，积极抑制催产素神经元的电活动。这种内源性阿片肽抑制的释放可能有助于分娩期间活动的增加，类似于吗啡戒断兴奋期间发生的情况。中枢阿片肽机制在分娩期间保留控制催产素神经元的能力，并且在不利的环境情况下，可以通过抑制催产素神经元的放电频率来中断已建立的分娩过程。
