Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release
Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release
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DOI：
10.1073/pnas.0403518101
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发表时间：
2004-07-13
影响因子：
11.1
通讯作者：
Llorens-Cortes, C
中科院分区：
文献类型：
--
作者：
De Mota, N;Goazigo, ARL;Llorens-Cortes, C
Apelin是一种近期分离出的神经肽，在视上核和室旁核中表达，作用于位于抗利尿激素能神经元上的特定受体。这些神经元的阶段性模式增强有助于在脱水或哺乳期间维持持续的抗利尿作用。在此，我们研究了apelin是否与精氨酸加压素（AVP）相互作用以维持体液内稳态。我们首先将内源性下丘脑和血浆apelin的主要分子形式鉴定为对应于apelin - 13，在较小程度上对应于apelin - 17。然后我们证明，在哺乳期大鼠中，apelin与抗利尿激素在视上核大细胞神经元中共定位，并且脑室内给予apelin可抑制抗利尿激素神经元的阶段性电活动。在哺乳期小鼠中，脑室内给予apelin - 17可降低血浆抗利尿激素水平并增加利尿作用。此外，禁水会增加全身性抗利尿激素释放并导致下丘脑抗利尿激素储备耗竭，降低血浆apelin浓度并诱导该肽在下丘脑积聚，这表明抗利尿激素和apelin呈反向调节，以促进全身性抗利尿激素释放并抑制利尿。抗利尿激素和apelin的相反作用可能通过自分泌调节抗利尿激素神经元的阶段性电活动而在下丘脑水平发生。总之，这些数据表明apelin是一种强效的利尿神经肽，通过抑制抗利尿激素神经元活动和抗利尿激素释放来对抗抗利尿激素的作用。apelin和抗利尿激素在大细胞神经元中的共存、它们相反的生物学效应以及调节作用可能在维持体液内稳态中起关键作用。
Apelin, a recently isolated neuropeptide that is expressed in the supraoptic and the paraventricular nuclei, acts on specific receptors located on vasopressinergic neurons. The increased phasic pattern of these neurons facilitates sustained antidiuresis during dehydration or lactation. Here, we investigated whether apelin interacts with arginine vasopressin (AVIP) to maintain body fluid homeostasis. We first characterized the predominant molecular forms of endogenous hypothalamic and plasma apelin as corresponding to apelin 13 and, to a lesser extent, to apelin 17. We then demonstrated that, in lactating rats, apelin was colocalized with AVP in supraoptic nucleus magnocellular neurons and given intracerebroventricularly inhibited the phasic electrical activity of AVP neurons. In lactating mice, intracerebroventricular administration of apelin 17 reduced plasma AVP levels and increased diuresis. Moreover, water deprivation, which increases systemic AVP release and causes depletion of hypothalamic AVP stores, decreased plasma apelin concentrations and induced hypothalamic accumulation of the pepticle, indicating that AVP and apelin are conversely regulated to facilitate systemic AVP release and suppress diuresis. Opposite effects of AVP and apelin are likely to occur at the hypothalamic level through autocrine modulation of the phasic electrical activity of AVP neurons. Altogether, these data demonstrate that apelin acts as a potent diuretic neuropepticle counteracting AVIP actions through inhibition of AVP neuron activity and AVP release. The coexistence of apelin and AVP in magnocellular neurons, their opposite biological effects, and regulation are likely to play a key role for maintaining body fluid homeostasis.