title: Angiotensin II contractile effects in mouse colon: role for pre- and post-junctional AT(1A)  receptors.
abstract: OBJECTIVE
  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, AT(1)  receptor antagonist, but not by PD123319, AT(2)  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, NK(1)  receptor antagonist, reduced the Ang II responses. Ondansetron, 5-HT(3)  receptor antagonist, SR48968, NK(2)  receptor antagonist, or hexamethonium, nicotinic receptor antagonist, were ineffective. The joint application of atropine and SR140333 produced no additive effect. Atropine reduced NK(1) -induced contraction. Transcripts encoding RAS components were detected in the colon samples. However, just AT(1A)  mRNA was expressed in both preparations, and AT(2)  mRNA was expressed only in the distal colon.
  
  
  CONCLUSIONS
  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 AT(1A)  receptors, the latter located on the enteric neurones, modulating the release of tachykinins and acetylcholine.
authors.affiliation: Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari (STEMBIO), Laboratorio di Fisiologia generale, Università di Palermo, Palermo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Mastropaolo
authors.forename: M G
authors.initials: MG
authors.lastname: Zizzo
authors.forename: F
authors.initials: F
authors.lastname: Mulè
authors.forename: R
authors.initials: R
authors.lastname: Serio
mesh_terms: D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018727:Muscarinic Antagonists; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II