Raggenbass M
Department of Physiology, University Medical Center, 1, rue Michel-Servet, CH-1211 Geneva 4, Switzerland.
Prog Neurobiol. 2001 Jun;64(3):307-26. doi: 10.1016/s0301-0082(00)00064-2.
During the last two decades, it has become apparent that vasopressin and oxytocin, in addition to playing a role as peptide hormones, also act as neurotransmitters/neuromodulators. A number of arguments support this notion: (i) vasopressin and oxytocin are synthesized not only in hypothalamo-neurohypophysial cells, but also in other hypothalamic and extrahypothalamic cell bodies, whose axon projects to the limbic system, the brainstem and the spinal cord. (ii) Vasopressin and oxytocin can be shed from central axons as are classical neurotransmitters. (iii) Specific binding sites, i.e. membrane receptors having high affinity for vasopressin and oxytocin are present in the central nervous system. (iv) Vasopressin and oxytocin can alter the firing rate of selected neuronal populations. (v) In-situ injection of vasopressin and oxytocin receptor agonists and antagonists can interfere with behavior or physiological regulations. Morphological studies and electrophysiological recordings have evidenced a close anatomical correlation between the presence of vasopressin and oxytocin receptors in the brain and the neuronal responsiveness to vasopressin or oxytocin. These compounds have been found to affect membrane excitability in neurons located in the limbic system, hypothalamus, circumventricular organs, brainstem, and spinal cord. Sharp electrode intracellular recordings and whole-cell recordings, done in brainstem motoneurons or in spinal cord neurons, have revealed that vasopressin and oxytocin can directly affect neuronal excitability by opening non-specific cationic channels or by closing K(+) channels. These neuropeptides can also influence synaptic transmission, by acting either postsynaptically or upon presynaptic target neurons or axon terminals. Whereas, in cultured neurons, vasopressin and oxytocin appear to mobilize intracellular Ca(++), in brainstem slices, the action of oxytocin is mediated by a second messenger that is distinct from the second messenger activated in peripheral target cells. In this review, we will summarize studies carried out at the cellular level, i.e. we will concentrate on in-vitro approaches. Vasopressin and oxytocin will be treated together. Though acting via distinct receptors in distinct brain areas, these two neuropeptides appear to exert similar effects upon neuronal excitability.
在过去二十年中，有一点变得很明显，即血管加压素和催产素除了作为肽类激素发挥作用外，还充当神经递质/神经调质。有许多论据支持这一观点：（i）血管加压素和催产素不仅在下丘脑 - 神经垂体细胞中合成，还在其他下丘脑和下丘脑外的细胞体中合成，这些细胞体的轴突投射到边缘系统、脑干和脊髓。（ii）血管加压素和催产素可以像经典神经递质一样从中枢轴突释放出来。（iii）中枢神经系统中存在特异性结合位点，即对血管加压素和催产素具有高亲和力的膜受体。（iv）血管加压素和催产素可以改变特定神经元群体的放电频率。（v）原位注射血管加压素和催产素受体激动剂和拮抗剂可以干扰行为或生理调节。形态学研究和电生理记录已经证明，大脑中血管加压素和催产素受体的存在与神经元对血管加压素或催产素的反应性之间存在密切的解剖学相关性。已经发现这些化合物会影响位于边缘系统、下丘脑、室周器官、脑干和脊髓中的神经元的膜兴奋性。在脑干运动神经元或脊髓神经元中进行的尖锐电极细胞内记录和全细胞记录表明，血管加压素和催产素可以通过打开非特异性阳离子通道或关闭钾离子通道直接影响神经元的兴奋性。这些神经肽还可以通过作用于突触后、突触前靶神经元或轴突终末来影响突触传递。然而，在培养的神经元中，血管加压素和催产素似乎会动员细胞内的钙离子，而在脑干切片中，催产素的作用是由一种与外周靶细胞中激活的第二信使不同的第二信使介导的。在这篇综述中，我们将总结在细胞水平上进行的研究，即我们将专注于体外研究方法。血管加压素和催产素将一起讨论。尽管这两种神经肽在不同的脑区通过不同的受体起作用，但它们似乎对神经元兴奋性产生相似的影响。
