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Dopamine outside the brain: The eye, cardiovascular system and endocrine pancreas.
Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2019-07-09 , DOI: 10.1016/j.pharmthera.2019.07.003
Claudio Bucolo 1 , Gian Marco Leggio 1 , Filippo Drago 1 , Salvatore Salomone 1
Affiliation  

Dopamine (DA) and DA receptors (DR) have been extensively studied in the central nervous system (CNS), but their role in the periphery is still poorly understood. Here we summarize data on DA and DRs in the eye, cardiovascular system and endocrine pancreas, three districts where DA and DA-related drugs have been studied and the expression of DR documented. In the eye, DA modulates ciliary blood flow and aqueous production, which impacts on intraocular pressure and glaucoma. In the cardiovascular system, DA increases blood pressure and heart activity, mostly through a stimulation of adrenoceptors, and induces vasodilatation in the renal circulation, possibly through D1R stimulation. In pancreatic islets, beta cells store DA and co-release it with insulin. D1R is mainly expressed in beta cells, where it stimulates insulin release, while D2R is expressed in both beta and delta cells (in the latter at higher level), where it inhibits, respectively, insulin and somatostatin release. The formation of D2R-somatostatin receptor 5 heteromers (documented in the CNS), might add complexity to the system. DA may exert both direct autocrine effects on beta cells, and indirect paracrine effects through delta cells and somatostatin. Bromocriptine, an FDA approved drug for diabetes, endowed with both D1R (antagonistic) and D2R (agonistic) actions, may exert complex effects, resulting from the integration of direct effects on beta cells and paracrine effects from delta cells. A full comprehension of peripheral DA signaling deserves further studies that may generate innovative therapeutic drugs to manage conditions such as glaucoma, cardiovascular diseases and diabetes.

中文翻译:

脑外多巴胺:眼睛,心血管系统和内分泌胰腺。

在中枢神经系统(CNS)中已经对多巴胺(DA)和DA受体(DR)进行了广泛的研究,但是对它们在周围环境中的作用仍知之甚少。在这里,我们总结了研究DA和DA相关药物并记录了DR表达的三个区域的眼睛,心血管系统和内分泌胰腺中DA和DR的数据。在眼中,DA调节睫状血流和水的产生,从而影响眼内压和青光眼。在心血管系统中,DA主要通过刺激肾上腺素能受体来增加血压和心脏活动,并可能通过D1R刺激引起肾脏循环中的血管舒张。在胰岛中,β细胞存储DA并与胰岛素共释放。D1R主要在β细胞中表达,可刺激胰岛素释放,而D2R在beta和delta细胞中均表达(后者处于较高水平),在D2R中它分别抑制胰岛素和生长抑素的释放。D2R-生长抑素受体5异聚体的形成(在CNS中有记载)可能会增加系统的复杂性。DA可能对β细胞产生直接自分泌作用,而对δ细胞和生长抑素也可能产生间接旁分泌作用。溴隐亭是FDA批准的糖尿病药物,具有D1R(拮抗作用)和D2R(激动作用),可能会产生复杂的作用,这是由于对β细胞的直接作用和来自δ细胞的旁分泌作用的综合作用所致。全面了解外周DA信号值得进一步研究,这些研究可能会产生创新的治疗药物来治疗诸如青光眼,心血管疾病和糖尿病等疾病。
更新日期:2019-11-18
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