Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, 58203, USA.
Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, 58203, USA.
Neuropharmacology. 2021 Jun 1;190:108565. doi: 10.1016/j.neuropharm.2021.108565. Epub 2021 Apr 20.
Arginine vasopressin (AVP) is a nonapeptide that serves as a neuromodulator in the brain and a hormone in the periphery that regulates water homeostasis and vasoconstriction. The subiculum is the major output region of the hippocampus and an integral component in the networks that processes sensory and motor cues to form a cognitive map encoding spatial, contextual, and emotional information. Whereas the subiculum expresses high densities of AVP-binding sites and AVP has been shown to increase the synaptic excitability of subicular pyramidal neurons, the underlying cellular and molecular mechanisms have not been determined. We found that activation of V receptors increased the excitability of subicular pyramidal neurons via activation of TRPV1 channels and depression of the GIRK channels. V receptor-induced excitation of subicular pyramidal neurons required the function of phospholipase Cβ, but was independent of intracellular Ca release. Protein kinase C was responsible for AVP-mediated depression of GIRK channels, whereas degradation of phosphatidylinositol 4,5-bisphosphate was involved in V receptor-elicited activation of TRPV1 channels. Our results may provide one of the cellular and molecular mechanisms to explain the physiological functions of AVP in the brain.
精氨酸加压素（AVP）是一种九肽，作为大脑中的神经调质和外周中的激素，调节水稳态和血管收缩。下托是海马体的主要输出区域，是处理感觉和运动线索以形成编码空间、上下文和情感信息的认知图的网络的组成部分。虽然下托表达高浓度的 AVP 结合位点，并且已经表明 AVP 增加了下托锥体神经元的突触兴奋性，但潜在的细胞和分子机制尚未确定。我们发现，通过激活 TRPV1 通道和抑制 GIRK 通道，V1 受体的激活增加了下托锥体神经元的兴奋性。V1 受体诱导的下托锥体神经元兴奋需要磷脂酶 Cβ 的功能，但不依赖于细胞内 Ca2+释放。蛋白激酶 C 负责 AVP 介导的 GIRK 通道抑制，而磷脂酰肌醇 4,5-二磷酸的降解参与 V1 受体诱导的 TRPV1 通道激活。我们的结果可能为解释 AVP 在大脑中的生理功能提供了一种细胞和分子机制。
