Aim: This study investigates whether a local renin–angiotensin system(RAS) exists in mouse colon and whether angiotensin II (Ang II) may playa role in the regulation of the contractile activity.Methods: Isometric recordings were performed in vitro on the longitudinalmuscle of mouse proximal and distal colon. Transcripts encoding forRAS components were investigated by RT-PCR.Results: Ang II caused, in both preparations, a concentration-dependentcontractile effect, antagonized by losartan, AT1 receptor antagonist, butnot by PD123319, AT2 receptor antagonist. The combination of losartanplus PD123319 caused no change on the Ang II-induced contraction thanlosartan alone. Tetrodotoxin, neural blocker, reduced the contractileresponse to Ang II in the proximal colon, whilst the response was abolishedin the distal colon. In both preparations, atropine, muscarinic receptorantagonist, or SR140333, NK1 receptor antagonist, reduced the Ang IIresponses. Ondansetron, 5-HT3 receptor antagonist, SR48968, NK2 receptorantagonist, or hexamethonium, nicotinic receptor antagonist, wereineffective. The joint application of atropine and SR140333 produced noadditive effect. Atropine reduced NK1-induced contraction. Transcriptsencoding RAS components were detected in the colon samples. However,just AT1A mRNA was expressed in both preparations, and AT2 mRNAwas expressed only in the distal colon.Conclusion: In the murine colon, local RAS may play a significant role inthe control of contractile activity. Ang II positively modulates thespontaneous contractile activity via activation of post-junctional andpre-junctional AT1A receptors, the latter located on the enteric neurones,modulating the release of tachykinins and acetylcholine.
|Numero di pagine||9|
|Stato di pubblicazione||Published - 2013|
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