Endothelin‐1 and its receptors on haemorrhoidal tissue: a potential site for therapeutic intervention

• Published in: British journal of pharmacology Vol. 174; no. 7; pp. 569 - 579
• Main Authors: Lohsiriwat, Varut, Scholefield, John H, Wilson, Vincent G, Dashwood, Michael R
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-04-2017; John Wiley and Sons Inc
• Subjects: Autoradiography; Binding Sites; Blotting, Western; Endothelin-1 - analysis; Endothelin-1 - metabolism; Hemorrhoids - drug therapy; Hemorrhoids - metabolism; Hemorrhoids - pathology; Hogs; Humans; Immunohistochemistry; Receptors, Endothelin - agonists; Receptors, Endothelin - analysis; Receptors, Endothelin - metabolism; Research Paper; Research Papers; Small intestine; Veins & arteries
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.13719

Background and Purpose
Haemorrhoids is a common anorectal condition affecting millions worldwide. We have studied the effect of endothelin‐1 (ET‐1) and the role of endothelin ETA and ETB receptors in haemorrhoid tissue.
Experimental Approach
Protein expression of ET‐1, ETA and ETB receptors 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.
Key Results
Dense binding of [125I]‐ET‐1 to haemorrhoidal sections was reduced by selective receptor antagonists. A higher density of ETB than ETA receptors was found in haemorrhoidal, than in control rectal tissue and confirmed by Western blot analysis. ETA and ETB receptors were localized to smooth muscle of haemorrhoidal arteries and veins, with ETB receptors on the endothelium. Human colonic and rectal arteries and veins were similarly sensitive to ET‐1 and affected by the ETA selective antagonist, but sarafotoxin S6a‐induced contractions were more pronounced in veins and antagonized by a selective ETB receptor antagonist.
Conclusions and Implications
ETA and ETB receptors are present in human haemorrhoids with ETB receptors predominating. ETA receptors 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 ETB receptors at low concentrations. Selective ETB agonists may have therapeutic potential to reduce congestion of the haemorrhoidal venous sinusoids.