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Activation of angiotensin II type 1 receptors and contractile activity in human sigmoid colon in vitro
Author(s) -
Mastropaolo M.,
Zizzo M. G.,
Auteri M.,
Caldara G.,
Liotta R.,
Mulè F.,
Serio R.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12538
Subject(s) - endocrinology , losartan , medicine , angiotensin ii , angiotensin ii receptor type 1 , receptor antagonist , receptor , angiotensin receptor , chemistry , myenteric plexus , biology , antagonist , immunohistochemistry
Aim To analyse the effects of angiotensin II (Ang II ) on the contractility of human sigmoid colon, and to characterize the subtype(s) of receptor(s) involved and the related action mechanism. Methods The contractility of sigmoid colon circular muscle strips was recorded isometrically. RT ‐ PCR and immunohistochemistry were used to reveal the eventual existence of a local renin–angiotensin system ( RAS ) and the distribution of Ang II receptors. Results Transcripts encoding for the Ang II type 1 ( AT 1 ) and the Ang II type 2 ( AT 2 ) receptor subtypes and for the angiotensin‐converting enzyme in the whole‐thickness muscular wall were observed. Ang II caused a concentration‐dependent contractile response, which is antagonized by losartan, AT 1 receptor antagonist, but not by PD 123319, AT 2 receptor antagonist. The joint application of losartan and PD 123319 did not produce any additive effect. The contractile response to Ang II was partially reduced by tetrodotoxin, Na + voltage‐gated neural channel blocker, and to some extent by SR 48968, tachykinin NK 2 receptor antagonist. However, hexamethonium, nicotinic receptor antagonist, atropine, cholinergic muscarinic receptor antagonist and SR 140333, tachykinin NK 1 receptor antagonist, were ineffective. Immunohistochemical analysis showed that AT 1 receptors were expressed on the smooth muscle layers and myenteric plexus. Conclusion Ang II positively modulates the spontaneous contractile activity of human sigmoid colon via activation of post‐junctional and pre‐junctional AT 1 receptors, the latter located on the enteric nerves that modulate the release of tachykinins. The presence of the components of RAS in the human colon suggests that Ang II can be also locally generated to control colonic motility.