Instituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC-CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina.
Department of Physiological Sciences, Institute of Biological and Health Sciences, Federal Rural University of Rio de Janeiro, Seropedica, Brazil.
J Neuroendocrinol. 2019 Apr;31(4):e12703. doi: 10.1111/jne.12703.
Angiotensin II (Ang II) acts on Ang II type 1 (AT1) receptors located in the organum vasculosum and subfornical organ (SFO) of the lamina terminalis as a main facilitatory mechanism of sodium appetite. The brain serotonin (5-HT) system with soma located in the dorsal raphe nucleus (DRN) provides a main inhibitory mechanism. In the present study, we first investigated the existence of Ang II AT1 receptors in serotonergic DRN neurones. Then, we examined whether whole body sodium depletion affects the gene expression of the AT1a receptor subtype and the presumed functional significance of AT1 receptors. Using confocal microscopy, we found that tryptophan hydroxylase-2 and serotonin neurones express AT1 receptors in the DRN. Immunofluorescence quantification showed a significant reduction in 5-HT content but no change in AT1 receptor expression or AT1/5-HT colocalisation in the DRN after sodium depletion. Whole body sodium depletion also significantly increased Agtr1a mRNA expression in the SFO and DRN. Oral treatment with the AT1 receptor antagonist losartan reversed the changes in Agtr1a expression in the SFO but not the DRN. Losartan injection into either the DRN or the mesencephalic aqueduct had no influence on sodium depletion-induced 0.3 mol L NaCl intake. The results indicate the expression of Agtr1a mRNA in the DRN and SFO as a marker of sodium depletion. They also suggest that serotonergic DRN neurones are targets for Ang II. However, the function of their AT1 receptors remains elusive.
血管紧张素 II（Ang II）作用于终板器官和下丘脑室旁核（SFO）中的血管紧张素 II 型 1（AT1）受体，是钠渴求的主要促进机制。位于中缝背核（DRN）的脑 5-羟色胺（5-HT）系统提供了主要的抑制机制。在本研究中，我们首先研究了 Ang II AT1 受体在 5-HT 能 DRN 神经元中的存在。然后，我们研究了全身钠耗竭是否会影响 AT1a 受体亚型的基因表达以及 AT1 受体的假定功能意义。使用共聚焦显微镜，我们发现色氨酸羟化酶-2 和 5-HT 神经元在 DRN 中表达 AT1 受体。免疫荧光定量显示，钠耗竭后 5-HT 含量显著降低，但 DRN 中 AT1 受体表达或 AT1/5-HT 共定位无变化。全身钠耗竭也显著增加了 SFO 和 DRN 中 Agtr1a mRNA 的表达。口服 AT1 受体拮抗剂氯沙坦可逆转 SFO 中 Agtr1a 表达的变化，但不能逆转 DRN 中的变化。氯沙坦注射到 DRN 或中脑导水管均对钠耗竭诱导的 0.3 mol/L NaCl 摄入没有影响。结果表明，DRN 和 SFO 中 Agtr1a mRNA 的表达是钠耗竭的标志物。它们还表明，5-HT 能 DRN 神经元是 Ang II 的靶标。然而，其 AT1 受体的功能仍不清楚。
