Hurbin Amandine, Orcel Hélène, Alonso Gérard, Moos Françoise, Rabié Alain
Centre National de la Recherche Scientifique-Unité Mixte de Recherche 5101, Biologie des Neurones Endocrines, Centre de Pharmacologie-Endocrinologie, Montpellier F-34094, France.
Endocrinology. 2002 Feb;143(2):456-66. doi: 10.1210/endo.143.2.8643.
Activity of the magnocellular neurons that synthesize vasopressin in the supraoptic and paraventricular nuclei of the hypothalamus is modulated by local release of the neuropeptide within the nuclei. V(1a) and V(1b) vasopressin receptor genes are expressed in these cells. The present study reports the localization of V(1a) and V(1b) receptors using multiple labeling immunocytochemistry. Both receptors are mainly located in vasopressinergic magnocellular neurons and colocalized with vasopressin in cytoplasmic vesicles dispersed throughout the cell. Possible functional modifications of the mRNA and protein levels of the V(1a) receptor, the major isoform, were also investigated by semiquantitative in situ hybridization and immunocytochemistry in rats submitted to reduced or increased water intake. V(1a) mRNA and receptor levels varied with water balance. V(1a) mRNA level dropped in rats submitted to high water intake. Conversely, dehydration up-regulated the V(1a) receptor content. These observations suggest that the pathways that regulate the expression of the genes encoding vasopressin and the V(1a) receptor are linked, which fits the present findings that the two partners are colocalized in cytoplasmic vesicles. Colocalization might explain how V(1) autoreceptors are controlled by cell activity and/or local concentration of vasopressin (released locally by the neurons themselves), allowing fine adjustment of magnocellular neuron activity.
在下丘脑视上核和室旁核中合成血管加压素的大细胞神经元的活动,受到神经肽在核内局部释放的调节。V(1a)和V(1b)血管加压素受体基因在这些细胞中表达。本研究报告了使用多重标记免疫细胞化学对V(1a)和V(1b)受体的定位。两种受体主要位于血管加压素能大细胞神经元中,并与血管加压素共定位于分散在整个细胞中的细胞质囊泡中。还通过半定量原位杂交和免疫细胞化学,对水摄入量减少或增加的大鼠中主要亚型V(1a)受体的mRNA和蛋白质水平可能的功能变化进行了研究。V(1a) mRNA和受体水平随水平衡而变化。高水摄入量的大鼠中V(1a) mRNA水平下降。相反,脱水上调了V(1a)受体含量。这些观察结果表明,调节血管加压素和V(1a)受体编码基因表达的途径是相关联的,这与目前这两个伙伴共定位于细胞质囊泡中的发现相符。共定位可能解释了V(1)自身受体如何受细胞活动和/或血管加压素局部浓度(由神经元自身局部释放)的控制,从而实现对大细胞神经元活动的精细调节。