Atrial natriuretic peptide (ANP) and its receptor are abundantly distributed in hypothalamic paraventricular nucleus (PVN), and contribute to regulation of corticotropin releasing factor (CRF) release in the brain. However, the mechanism by which ANP regulates the activity of PVN CRFergic neurons remains unclear. Here, we investigated the mechanism by which ANP modulates the neuronal activity related to PVN CRF-mRNA expression in vitro in mice using whole-cell patch-clamp recording, single-cell RT-PCR, immunofluorescence, and pharmacological methods. Our data demonstrated that ANP significantly reduced the membrane excitability of PVN neurons expressing CRF-mRNA. This effect was abolished by an antagonist of ANP receptor A (NPR - A), namely A71915. Furthermore, ANP significantly suppressed the hyperpolarization - activated cationic currents (I_h) of neurons expressing CRF-mRNA. Blockade of either I_h or NPR - A completely prevented this inhibitory effect. Immunohistochemistry results indicated that NPR - A immunoreactivity was present in PVN CRF-positive neurons. These findings suggest that ANP decreases the excitability of PVN CRFergic neurons via NPR - A - mediated inhibition of I_h channel activity in vitro in mice.

2024-06-01·Heliyon

Liraglutide ameliorates TAC-induced cardiac hypertrophy and heart failure by upregulating expression level of ANP expression

Article

作者: Xu, Zhenjun ; Pan, Jun ; Wang, Dongjin ; Zhang, Keyin ; Liu, Wenxue ; Li, Kai ; Li, Ruisha ; Yu, Yanrong

Recent studies have underscored the cardioprotective properties of liraglutide. This research explores its impact on cardiac hypertrophy and heart failure following transverse aortic constriction (TAC). We found that liraglutide administration markedly ameliorated cardiac hypertrophy, fibrosis, and function. These benefits correlated with increased ANP expression and reduced activity in the calcineurin A/NFATc3 signaling pathway. Moreover, liraglutide mitigated ER stress and cardiomyocyte apoptosis, and enhanced autophagy. Notably, the positive effects of liraglutide diminished when co-administered with A71915, an ANP inhibitor, suggesting that ANP upregulation is critical to its cardioprotective mechanism.

2023-08-01·Journal of Cerebral Blood Flow & Metabolism

Reversal of the detrimental effects of social isolation on ischemic cerebral injury and stroke-associated pneumonia by inhibiting small intestinal γδ T-cell migration into the brain and lung

Article

作者: Yuan, Shiying ; Hashimoto, Kenji ; Han, Mengqi ; Zhang, Jiancheng ; Shang, You ; Chen, Xiaoyan ; Wang, Mengyuan ; Zhang, Yujing ; Yu, Yuan ; Xie, Bing ; Wu, Yuming

Social isolation (ISO) is associated with an increased risk and poor outcomes of ischemic stroke. However, the roles and mechanisms of ISO in stroke-associated pneumonia (SAP) remain unclear. Adult male mice were single- or pair-housed with an ovariectomized female mouse and then subjected to transient middle cerebral artery occlusion. Isolated mice were treated with the natriuretic peptide receptor A antagonist A71915 or anti-gamma-delta (γδ) TCR monoclonal antibody, whereas pair-housed mice were treated with recombinant human atrial natriuretic peptide (rhANP). Subdiaphragmatic vagotomy (SDV) was performed 14 days before single- or pair-housed conditions. We found that ISO significantly worsened brain and lung injuries relative to pair housing, which was partially mediated by elevated interleukin (IL)-17A levels and the migration of small intestine-derived inflammatory γδ T-cells into the brain and lung. However, rhANP treatment or SDV could ameliorate ISO-exacerbated post-stroke brain and lung damage by reducing IL-17A levels and inhibiting the migration of inflammatory γδ T-cells into the brain and lung. Our results suggest that rhANP mitigated ISO-induced exacerbation of SAP and ischemic cerebral injury by inhibiting small intestine-derived γδ T-cell migration into the lung and brain, which could be mediated by the subdiaphragmatic vagus nerve.

100 项与 A-71915 相关的药物交易

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