Investigation of the distribution and function of alpha-adrenoceptors in the sheep isolated internal anal sphincter.

British Journal of Pharmacology
S RaymentV G Wilson

Abstract

We have investigated the distribution of alpha-adrenoceptors in sheep internal anal sphincter (IAS), as a model for the human tissue, and evaluated various imidazoline derivatives for potential treatment of faecal incontinence. Saturation and competition binding with (3)H-prazosin and (3)H-RX821002 were used to confirm the presence and density of alpha-adrenoceptors in sheep IAS, and the affinity of imidazoline compounds at these receptors. A combination of in vitro receptor autoradiography and immunohistochemistry was used to investigate the regional distribution of binding sites. Contractile activity of imidazoline-based compounds on sheep IAS was assessed by isometric tension recording. Saturation binding confirmed the presence of both alpha(1)- and alpha(2)-adrenoceptors, and subsequent characterization with sub-type-selective agents, identified them as alpha(1A)- and alpha(2D)-adrenoceptor sub-types. Autoradiographic studies with (3)H-prazosin showed a positive association of alpha(1)-adrenoceptors with immunohistochemically identified smooth muscle fibres. Anti-alpha(1)-adrenoceptor immunohistochemistry revealed similar distributions of the receptor in sheep and human IAS. The imidazoline compounds caused concentration-de...Continue Reading

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Citations

Nov 19, 2003·Langenbeck's Archives of Surgery·A G Acheson, J H Scholefield
Jun 7, 2003·Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland·N GriffinJ H Scholefield
Mar 9, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Varut LohsiriwatVincent G Wilson
Mar 5, 2019·Journal of Neurogastroenterology and Motility·Kathleen D Keef, Caroline A Cobine
Jun 7, 2014·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·S J RaymentV G Wilson

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