Interaction between the Renin–Angiotensin System and Enteric Neurotransmission Contributes to Colonic Dysmotility in the TNBS-Induced Model of Colitis

International Journal of Molecular Sciences

Patrícia Dias-Pereira¹  Margarida Duarte-Araújo²  MiguelA. Faria²  Mariana Ferreira-Duarte³  Manuela Morato³  MariaSofia Rocha³  Daniela Menezes-Pinto³  Tiago Rodrigues-Pinto³  Marisa Esteves-Monteiro³  Fernando Magro⁴  Teresa Sousa⁴ 

[1] Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal;LAQV-REQUIMTE, Faculty of Pharmacy of University of Porto (FFUP), 4050-313 Porto, Portugal;Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy of University of Porto (FFUP), 4050-313 Porto, Portugal;Unit of Pharmacology and Therapeutics, Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal;

关键词: inflammatory bowel disease;    IBD;    TNBS-induced colitis;    colonic dysmotility;    angiotensin II;    AT₁ and AT₂ receptors;   

DOI  :  10.3390/ijms22094836

来源: DOAJ

【 摘 要 】

Angiotensin II (Ang II) regulates colon contraction, acting not only directly on smooth muscle but also indirectly, interfering with myenteric neuromodulation mediated by the activation of AT₁ /AT₂ receptors. In this article, we aimed to explore which mediators and cells were involved in Ang II-mediated colonic contraction in the TNBS-induced rat model of colitis. The contractile responses to Ang II were evaluated in distinct regions of the colon of control animals or animals with colitis in the absence and presence of different antagonists/inhibitors. Endogenous levels of Ang II in the colon were assessed by ELISA and the number of AT₁/AT₂ receptors by qPCR. Ang II caused AT₁ receptor-mediated colonic contraction that was markedly decreased along the colons of TNBS-induced rats, consistent with reduced AT₁ mRNA expression. However, the effect mediated by Ang II is much more intricate, involving (in addition to smooth muscle cells and nerve terminals) ICC and EGC, which communicate by releasing ACh and NO in a complex mechanism that changes colitis, unveiling new therapeutic targets.

【 授权许可】

Unknown