title: Activation of angiotensin II type 1 receptors and contractile activity in human sigmoid colon in vitro.
abstract: OBJECTIVE
  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 (AT1 ) and the Ang II type 2 (AT2 ) 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, AT1 receptor antagonist, but not by PD123319, AT2 receptor antagonist. The joint application of losartan and PD123319 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 SR48968, tachykinin NK2 receptor antagonist. However, hexamethonium, nicotinic receptor antagonist, atropine, cholinergic muscarinic receptor antagonist and SR140333, tachykinin NK1 receptor antagonist, were ineffective. Immunohistochemical analysis showed that AT1 receptors were expressed on the smooth muscle layers and myenteric plexus.
  
  
  CONCLUSIONS
  Ang II positively modulates the spontaneous contractile activity of human sigmoid colon via activation of post-junctional and pre-junctional AT1 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.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Laboratorio di Fisiologia generale, Palermo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Mastropaolo
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Laboratorio di Fisiologia generale, Palermo, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Zizzo
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Laboratorio di Fisiologia generale, Palermo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Auteri
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Laboratorio di Fisiologia generale, Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Caldara
authors.affiliation: Pathology Service, Department of Diagnostic and Therapeutic Services, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Liotta
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Laboratorio di Fisiologia generale, Palermo, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Mulè
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Laboratorio di Fisiologia generale, Palermo, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Serio
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000494:pharmacology*; D012809:Colon, Sigmoid / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
chemical_list: D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319; D007703:Peptidyl-Dipeptidase A
keywords: angiotensin II; angiotensin II type 1 receptors; human colon; intestinal motility; tachykinins