Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK.
J Neuroendocrinol. 2010 Apr;22(4):301-8. doi: 10.1111/j.1365-2826.2010.01968.x. Epub 2010 Jan 27.
The expression of the novel peptide apelin and its receptor APJ within specific regions of the brain, in particular the magnocellular neurones of the hypothalamus and the circumventricular organs, has implicated the apelinergic system in mechanisms controlling fluid homeostasis. In addition, apelin and APJ are considered to be involved in controlling arginine vasopressin (AVP) secretion into the circulation and release within the hypothalamic-neurohypophysial system. To clarify the role of APJ during regulation of fluid homeostasis, we compared the effects of osmotic stimulation on the urinary concentrating capacities and central nervous system responses of salt-loaded (SL) and water-deprived (WD) female APJ knockout (APJ(-/-)) mice and wild-type controls. SL resulted in a significantly increased urine volume in APJ(-/-) mice compared to wild-type controls, whereas WD in APJ(-/-) mice failed to reduce urine volume as seen in wild-type controls. AVP transcripts in the supraoptic and paraventricular nuclei and plasma AVP concentrations were significantly attenuated in SL APJ(-/-) mice compared to SL wild-type, but increased comparably in wild-type and APJ(-/-) mice after WD. Analysis of c-fos mRNA expression in the median preoptic nucleus and subfornical organ in response to either WD or SL showed attenuated expression in APJ(-/-) compared to wild-type mice. These findings further implicate the apelinergic system in mechanisms controlling fluid homeostasis, particularly at a neuroendocrine level, and suggest stimulus-specific involvement in vasopressinergic activity.
新型肽类阿片素及其受体 APJ 在大脑特定区域(尤其是下丘脑的大细胞神经元和室周器官)的表达表明,阿片素能系统参与了控制液体平衡的机制。此外,阿片素和 APJ 被认为参与控制精氨酸血管加压素(AVP)分泌到循环中,并在下丘脑-神经垂体系统中释放。为了阐明 APJ 在调节液体平衡中的作用,我们比较了盐负荷(SL)和水剥夺(WD)雌性 APJ 敲除(APJ(-/-))小鼠和野生型对照的渗透刺激对尿浓缩能力和中枢神经系统反应的影响。与野生型对照相比,SL 导致 APJ(-/-) 小鼠的尿量显著增加,而 WD 导致 APJ(-/-) 小鼠的尿量没有像野生型对照那样减少。SL APJ(-/-) 小鼠的视上核和室旁核的 AVP 转录物和血浆 AVP 浓度明显低于 SL 野生型,但 WD 后野生型和 APJ(-/-) 小鼠的 AVP 转录物增加幅度相当。对 WD 或 SL 反应的中前脑核和穹窿下器官中 c-fos mRNA 表达的分析表明,APJ(-/-) 小鼠的表达低于野生型小鼠。这些发现进一步表明阿片素能系统参与了控制液体平衡的机制,特别是在神经内分泌水平上,并表明在血管加压素能活性中存在刺激特异性参与。