Margaret R MacLean, Barry Fanburg, Nicolas Hill, Howard M Lazarus, Thomas F Pack, Michelle Palacios, Krishna C Penumatsa, Stephen A Wring
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Abstract
Serotonin is often referred to as a "happy hormone" as it maintains good mood, well-being, and happiness. It is involved in communication between nerve cells and plays a role in sleeping and digestion. However, too much serotonin can have pathogenic effects and serotonin synthesis is elevated in pulmonary artery endothelial cells from patients with pulmonary arterial hypertension (PAH). PAH is characterized by elevated pulmonary pressures, right ventricular failure, inflammation, and pulmonary vascular remodeling; serotonin has been shown to be associated with these pathologies. The rate-limiting enzyme in the synthesis of serotonin in the periphery of the body is tryptophan hydroxylase 1 (TPH1). TPH1 expression and serotonin synthesis are elevated in pulmonary artery endothelial cells in patients with PAH. The serotonin synthesized in the pulmonary arterial endothelium can act on the adjacent pulmonary arterial smooth muscle cells (PASMCs), adventitial macrophages, and fibroblasts, in a paracrine fashion. In humans, serotonin enters PASMCs cells via the serotonin transporter (SERT) and it can cooperate with the 5-HT1B receptor on the plasma membrane; this activates both contractile and proliferative signaling pathways. The "serotonin hypothesis of pulmonary hypertension" arose when serotonin was associated with PAH induced by diet pills such as fenfluramine, aminorex, and chlorphentermine; these act as indirect serotonergic agonists causing the release of serotonin from platelets and cells through the SERT. Here the role of serotonin in PAH is reviewed. Targeting serotonin synthesis or signaling is a promising novel alternative approach which may lead to novel therapies for PAH. © 2022 American Physiological Society. Compr Physiol 12: 1-16, 2022.
羟色胺与肺动脉高压;性与药物以及 ROCK 与 Rho。
羟色胺通常被称为 "快乐激素",因为它能保持良好的情绪、幸福和快乐。它参与神经细胞之间的交流,并在睡眠和消化中发挥作用。然而,过多的血清素会产生致病作用,肺动脉高压(PAH)患者的肺动脉内皮细胞中的血清素合成会升高。肺动脉高压的特点是肺压升高、右心室衰竭、炎症和肺血管重塑;血清素已被证明与这些病症有关。在人体外周合成血清素的限速酶是色氨酸羟化酶 1(TPH1)。在 PAH 患者的肺动脉内皮细胞中,TPH1 的表达和血清素的合成都会升高。肺动脉内皮细胞合成的血清素可通过旁分泌方式作用于邻近的肺动脉平滑肌细胞(PASMC)、临近的巨噬细胞和成纤维细胞。在人体中,血清素通过血清素转运体(SERT)进入 PASMCs 细胞,并与质膜上的 5-HT1B 受体合作,从而激活收缩和增殖信号通路。5-羟色胺与芬氟拉明、阿米诺雷克斯和氯苯特明等减肥药诱发的 PAH 有关,从而提出了 "5-羟色胺肺动脉高压假说";这些减肥药是间接的 5-羟色胺能激动剂,可通过 SERT 从血小板和细胞中释放 5-羟色胺。在此回顾一下血清素在 PAH 中的作用。以血清素合成或信号传导为靶点是一种很有前景的新型替代方法,可为 PAH 带来新型疗法。© 2022 美国生理学会。Compr Physiol 12: 1-16, 2022.
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