Llorens-Cortes Catherine, Moos Françoise
INSERM, U 691, Paris, France.
Prog Brain Res. 2008;170:559-70. doi: 10.1016/S0079-6123(08)00443-3.
This review concentrates on the characteristics and functionality of endocrine neurons in the hypothalamo-neurohypophysial system, coexpressing two peptides, vasopressin and apelin. Vasopressin is synthesized in the soma of magnocellular neurons, then packaged in granules with its respective receptors. In these neurons, apelin is generated from a larger precursor proapelin and is detected in vesicles, some of them colocalize with vasopressin, for others there is a marked segregation of apelin and vasopressin immunoreactivity along the hypothalamo-hypophyseal axons. Furthermore, apelin receptors, like V1a-type and V1b-type vasopressin receptors, are synthesized by magnocellular vasopressin neurons. In lactating rodents, apelin given intracerebroventricularly inhibited the phasic electrical activity of vasopressin neurons, reduced plasma vasopressin levels and increased aqueous diuresis, showing that apelin acts as a potent diuretic neuropeptide, counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release. Moreover, in response to potent physiological stimuli known to evoke increased phasic activity of vasopressin neurons (hyper-osmolarity like during dehydration), both the soma dendrites and neurohypophysial terminals loose their dense staining quality, and vasopressin is released by (i) dendrites in the extracellular space to optimize the characteristic phasic activity necessary to a sustained release of vasopressin and (ii) by terminals in blood circulation where vasopressin then ensures its main endocrine actions at kidney level (antidiuretic effect). Conversely, apelin accumulates in these neurons rather than being released into the bloodstream and probably into the nuclei. Thus, decreases in the local supply of apelin to magnocellular vasopressin cell bodies may facilitate the expression by vasopressin neurons of an optimized phasic activity, by decreasing the inhibitory actions of apelin on these neurons. Antagonistic regulation of apelin and vasopressin has a biological purpose, making it possible to maintain the water balance of the organism by preventing additional water loss via kidneys. This reveals a new physiological concept of dual and opposite functional potentiality for endocrine neurons coexpressing different neuropeptides in separate vesicles: depending on the degree of their electrical activation/inhibition, neurons release selectively the very coexpressed peptides that will ensure its accurate endocrine functions in perfect accordance with the hormonal demand.
本综述着重探讨下丘脑 - 神经垂体系统中共同表达两种肽（血管加压素和阿片肽）的内分泌神经元的特征和功能。血管加压素在大细胞神经元的胞体中合成，然后与各自的受体一起包装在颗粒中。在这些神经元中，阿片肽由较大的前体前阿片肽产生，并在小泡中被检测到，其中一些小泡与血管加压素共定位，而在其他小泡中，阿片肽和血管加压素免疫反应性沿着下丘脑 - 垂体轴突有明显的分离。此外，阿片肽受体，如V1a型和V1b型血管加压素受体，由大细胞血管加压素神经元合成。在哺乳期啮齿动物中，脑室内注射阿片肽可抑制血管加压素神经元的阶段性电活动，降低血浆血管加压素水平并增加水利尿，表明阿片肽作为一种有效的利尿神经肽，通过抑制血管加压素神经元活动和血管加压素释放来抵消血管加压素的作用。此外，在已知会引起血管加压素神经元阶段性活动增加（如脱水时的高渗状态）的强烈生理刺激下，胞体树突和神经垂体终末都会失去其浓密的染色特性，血管加压素通过以下方式释放：（i）树突将其释放到细胞外空间，以优化持续释放血管加压素所需的特征性阶段性活动；（ii）终末将其释放到血液循环中，血管加压素随后在肾脏水平发挥其主要内分泌作用（抗利尿作用）。相反，阿片肽在这些神经元中积累而不是释放到血液中，可能也释放到细胞核中。因此，大细胞血管加压素细胞体局部阿片肽供应的减少可能通过减少阿片肽对这些神经元的抑制作用，促进血管加压素神经元表达优化的阶段性活动。阿片肽和血管加压素的拮抗调节具有生物学目的，即通过防止经肾脏额外失水来维持机体的水平衡。这揭示了一个新的生理学概念，即共同表达不同神经肽的内分泌神经元在不同小泡中具有双重且相反的功能潜力：根据其电激活/抑制程度，神经元选择性地释放共同表达的肽，以确保其精确的内分泌功能与激素需求完美匹配。
