Authors: acheson, a.¹; rayment, s.²; eames, t.¹; mundey, m.²; nisar, p.¹; scholefield, j¹; wilson, v. g.²

Source: Neurogastroenterology and Motility, Volume 21, Number 3, March 2009 , pp. 335-345(11)

Publisher: Wiley-Blackwell

Abstract:

 

Nitric oxide is widely established as an important neurotransmitter in the control of anal sphincter tone; although, a number of other transmitters have also been tentatively implicated. Whilst α-adrenoceptor antagonists reduce anal sphincter pressure in man, the role of noradrenaline as a possible transmitter is poorly characterised. We have investigated the contribution of these transmitters to neurogenic relaxations, and evaluated the possible role of a non-nitrergic, non-adrenergic transmitter. The magnitude and duration of neurogenic responses were examined by measuring responses to electrical field stimulation (EFS) in segments of sheep internal anal sphincter following the development of spontaneous myogenic tone. Neurogenic relaxations induced by EFS were significantly reduced in the presence of N^G-nitro-L-arginine methyl ester (l-NAME) suggesting major involvement of nitric oxide as a neurotransmitter. The duration of neurogenic relaxations was inversely related to the frequency of EFS, with contractile responses often manifest at higher frequencies. The duration of relaxations at high frequencies of EFS was increased by bretylium (adrenergic neurone blocker) and prazosin (α₁-adrenoceptor antagonist). At higher frequencies of EFS, 60% of preparations also produced a residual non-nitrergic, non-adrenergic, apamin-sensitive relaxation which was unaffected by vasoactive intestinal polypeptide (VIP) and inhibitors of purinergic responses [suramin, pyridoxal-phosphate-6-azophenyl 2′,4′ disulfonic acid (PPADS) and α,β-methylene adenosine triphosphate (ATP)]. However, MRS2179 (P2Y₁ receptor antagonist) showed a modest inhibitory effect. We conclude that endogenous noradrenaline acts via postjunctional α₁-adrenoceptors to antagonize neurogenic relaxations that are largely mediated by nitric oxide. Our results indicate the involvement of a non-nitrergic, non-adrenergic, apamin-sensitive transmitter which is inhibited by MRS2179, suggesting a possible role for purines.

Keywords: anal sphincter; electrical field stimulation; neurotransmission; noradrenaline

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2982.2008.01250.x

Affiliations: 1: Department of Surgery, The University of Nottingham Medical School, Queen's Medical Centre, Clifton Boulevard, Nottingham, United Kingdom 2: School of Biomedical Sciences, The University of Nottingham Medical School, Queen's Medical Centre, Clifton Boulevard, Nottingham, United Kingdom

Publication date: 2009-03-01

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