title: Endothelin-1 and its receptors on haemorrhoidal tissue: a potential site for therapeutic intervention.
abstract: Haemorrhoids is a common anorectal condition affecting millions worldwide. We have studied the effect of endothelin-1 (ET-1) and the role of endothelin ETAand ETBreceptors in haemorrhoid tissue.
  
  
  
  Protein expression of ET-1, ETAand ETBreceptors were compared between haemorrhoids and normal rectal submucosa using Western blot analysis, with the localization of proteins determined by autoradiography and immunohistochemistry. Effects of ET-1 and sarafotoxin 6a on human colonic and rectal arteries and veins was assessed by wire myography and the involvement of receptor subtypes established by selective antagonists.
  
  
  
  Dense binding of [125I]-ET-1 to haemorrhoidal sections was reduced by selective receptor antagonists. A higher density of ETBthan ETAreceptors was found in haemorrhoidal, than in control rectal tissue and confirmed by Western blot analysis. ETAand ETBreceptors were localized to smooth muscle of haemorrhoidal arteries and veins, with ETBreceptors on the endothelium. Human colonic and rectal arteries and veins were similarly sensitive to ET-1 and affected by the ETAselective antagonist, but sarafotoxin S6a-induced contractions were more pronounced in veins and antagonized by a selective ETBreceptor antagonist.
  
  
  
  ETAand ETBreceptors are present in human haemorrhoids with ETBreceptors predominating. ETAreceptors are activated by ET-1 to mediate a contraction in arteries and veins, but the latter are selectively activated by sarafotoxin S6a - a response that involves ETBreceptors at low concentrations. Selective ETBagonists may have therapeutic potential to reduce congestion of the haemorrhoidal venous sinusoids.
authors.affiliation: Division of Gastrointestinal Surgery, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
authors.forename: Varut
authors.initials: V
authors.lastname: Lohsiriwat
authors.affiliation: Division of Gastrointestinal Surgery, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
authors.forename: John H
authors.initials: JH
authors.lastname: Scholefield
authors.affiliation: School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Wilson
authors.affiliation: Royal Free Hospital Campus, University College Medical School, London, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Dashwood
mesh_terms: D001345:Autoradiography; D001665:Binding Sites; D015153:Blotting, Western; D019332:Endothelin-1 / Q000032:analysis / Q000378:metabolism*; D006484:Hemorrhoids / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017466:Receptors, Endothelin / Q000819:agonists / Q000032:analysis / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D017466:Receptors, Endothelin