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- Title
Interaction between the Renin–Angiotensin System and Enteric Neurotransmission Contributes to Colonic Dysmotility in the TNBS-Induced Model of Colitis.
- Authors
Ferreira-Duarte, Mariana; Rodrigues-Pinto, Tiago; Sousa, Teresa; Faria, Miguel A.; Rocha, Maria Sofia; Menezes-Pinto, Daniela; Esteves-Monteiro, Marisa; Magro, Fernando; Dias-Pereira, Patrícia; Duarte-Araújo, Margarida; Morato, Manuela; Eguchi, Satoru
- Abstract
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.
- Subjects
RENIN-angiotensin system; COLITIS; INFLAMMATORY bowel diseases; ANGIOTENSIN II; DRUG target; NEURAL transmission; NEURONS
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 9, p4836
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22094836