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Angiotensin II contractile effects in mouse colon: role for pre- and post-junctional AT(1A) receptors

M Mastropaolo1, M G Zizzo, F Mulè

  • 1Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari (STEMBIO), Laboratorio di Fisiologia generale, Università di Palermo, Palermo, Italy.

Acta Physiologica (Oxford, England)
|November 23, 2012
PubMed
Abstract

Insights

The mouse colon has a local renin-angiotensin system (RAS). Angiotensin II (Ang II) activates AT(1A) receptors to modulate colon contractile activity through neural pathways.

Area of Science:

  • Gastroenterology
  • Physiology
  • Pharmacology

Background:

  • The renin-angiotensin system (RAS) is crucial for cardiovascular regulation.
  • Its role in gastrointestinal motility, particularly in the colon, is less understood.

Purpose of the Study:

  • To determine if a local RAS exists in the mouse colon.
  • To investigate the role of angiotensin II (Ang II) in regulating colon contractile activity.

Main Methods:

  • Isometric tension recordings of longitudinal muscle from mouse proximal and distal colon.
  • RT-PCR to detect transcripts of RAS components.
  • Pharmacological blockade of specific receptors (AT(1), AT(2), NK(1), muscarinic, 5-HT(3), nicotinic).

Main Results:

  • Ang II induced concentration-dependent contractions, blocked by the AT(1) receptor antagonist losartan.
  • Neural pathways were involved, with tetrodotoxin reducing Ang II responses in the proximal colon and abolishing them in the distal colon.
  • AT(1A) mRNA was detected in both colon segments, while AT(2) mRNA was found only in the distal colon.
  • Ang II modulated contractile activity via AT(1A) receptors on post-junctional sites and pre-junctional sites on enteric neurons, influencing acetylcholine and tachykinin release.

Conclusions:

  • A local RAS is present in the murine colon.
  • Ang II plays a significant role in controlling colon contractile activity.
  • AT(1A) receptor activation mediates Ang II's effects on colonic motility.

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