AT1 receptors mediate contractile effects of Angiotensin II on mouse colon

Abstract

Angiotensin II (Ang II) is a potent smooth muscle contractile neurohumoral agonist via interaction with AT1 and AT2 receptors. Although these receptors are well expressed in the gut, very little research has been devoted to analysed the physiological role played by Ang II (and its receptors) in the regulation of gastrointestinal motility. The effects of Ang II on mouse proximal and distal colon contractility, the receptor subtypes involved were investigated in vitro, using the organ bath technique. Longitudinally-oriented segments from mouse proximal and distal colon displayed ongoing contractile activity, characterized by phasic contractions. Ang II induced a concentration-dependent muscular contraction in both preparations, reduced by the neural blocker, tetrodotoxin, by the AT1 receptor antagonist, losartan, but not affected by the AT2 receptor antagonist, PD123319. SR140333, a tachykinin NK1 receptor antagonist, antagonized the excitatory effects induced by Ang II in the proximal but not in the distal colon, whilst atropine, muscarinic receptor antagonist, antagonized the contractile effects to Ang II only in the distal colon. In conclusion, in the murine colon Ang II positively modulates the spontaneous contractile activity, via activation of post-junctional AT1 receptors and of pre-junctional AT1 receptors on tachykinergic neurons in the proximal colon and on cholinergic neurons in the distal colon, regulating neurotransmitter release.