Angiotensin II contractile effects in mouse colon: role for pre- and post-junctional AT1A receptors

Aim: This study investigates whether a local renin–angiotensin system (RAS) exists in mouse colon and whether angiotensin II (Ang II) may play a role in the regulation of the contractile activity. Methods: Isometric recordings were performed in vitro on the longitudinal muscle of mouse proximal and distal colon. Transcripts encoding for RAS components were investigated by RT-PCR. Results: Ang II caused, in both preparations, a concentration-dependent contractile effect, antagonized by losartan, AT1 receptor antagonist, but not by PD123319, AT2 receptor antagonist. The combination of losartan plus PD123319 caused no change on the Ang II-induced contraction than losartan alone. Tetrodotoxin, neural blocker, reduced the contractile response to Ang II in the proximal colon, whilst the response was abolished in the distal colon. In both preparations, atropine, muscarinic receptor antagonist, or SR140333, NK1 receptor antagonist, reduced the Ang II responses. Ondansetron, 5-HT3 receptor antagonist, SR48968, NK2 receptor antagonist, or hexamethonium, nicotinic receptor antagonist, were ineffective. The joint application of atropine and SR140333 produced no additive effect. Atropine reduced NK1-induced contraction. Transcripts encoding RAS components were detected in the colon samples. However, just AT1A mRNA was expressed in both preparations, and AT2 mRNA was expressed only in the distal colon. Conclusion: In the murine colon, local RAS may play a significant role in the control of contractile activity. Ang II positively modulates the spontaneous contractile activity via activation of post-junctional and pre-junctional AT1A receptors, the latter located on the enteric neurones, modulating the release of tachykinins and acetylcholine.