Involvement of dopaminergic signaling in the cross talk between the renin-angiotensin system and inflammation
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REVIEW
Involvement of dopaminergic signaling in the cross talk between the renin-angiotensin system and inflammation Javier Campos 1
&
Rodrigo Pacheco 1,2
Received: 31 January 2020 / Accepted: 25 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The renin-angiotensin system (RAS) is a fundamental regulator of blood pressure and has emerged as an important player in the control of inflammatory processes. Accordingly, imbalance on RAS components either systemically or locally might trigger the development of inflammatory disorders by affecting immune cells. At the same time, alterations in the dopaminergic system have been consistently involved in the physiopathology of inflammatory disorders. Accordingly, the interaction between the RAS and the dopaminergic system has been studied in the context of inflammation of the central nervous system (CNS), kidney, and intestine, where they exert antagonistic actions in the regulation of the immune system. In this review, we summarized, integrated, and discussed the cross talk of the dopaminergic system and the RAS in the regulation of inflammatory pathologies, including neurodegenerative disorders, such as Parkinson’s disease. We analyzed the molecular mechanisms underlying the interaction between both systems in the CNS and in systemic pathologies. Moreover, we also analyzed the impact of the commensal microbiota in the regulation of RAS and dopaminergic system and how it is involved in inflammatory disorders. Furthermore, we summarized the therapeutic approaches that have yielded positive results in preclinical or clinical studies regarding the use of drugs targeting the RAS and dopaminergic system for the treatment of inflammatory conditions. Further understanding of the molecular and cellular regulation of the RAS-dopaminergic cross talk should allow the formulation of new therapies consisting of novel drugs and/or repurposing already existing drugs, alone or in combination, for the treatment of inflammatory disorders. Keywords Renin-angiotensin system . Dopamine . Inflammatory disorders . Parkinson’s disease . Inflammatory bowel diseases . Chronic kidney disease
Abbreviations ACE Angiotensin-converting enzyme AngI Angiotensin I AngII Angiotensin II Ang(1–7) Angiotensin (1–7) ATR1 Type 1 AngII receptor ATR2 Type 2 AngII receptor CNS Central nervous system COMPT Catechol-O-methyltransferase DRDn Dopamine receptor Dn This article is a contribution to the special issue on: Neuro-immune Interactions - Guest Editor: David Farrar
DSS IBD IL-n MasR MPTP RAS Thn TH TNF-α WT βAR β2AR 6-OHDA
Dextran sodium sulfate Inflammatory bowel diseases Interleukin n Mas receptor 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Renin-angiotensin system T-helper n Tyrosine hydroxylase Tumor necrosis factor α Wild-type β-adrenergic receptor β2-adrenergic receptor 6-hydroxydopamine
* Rodrigo Pacheco [email protected]
Introduction 1
Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Av. Zañartu 1482, 7780272 Ñuñoa, Santiago, Chile
2
Unive
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