Regulation of nerve-evoked contractions of rabbit vas deferens by acetylcholine.

Audrey Wallace,Deborah Gabriel,Noel G Mchale,Mark A Hollywood,Keith D Thornbury,Gerard P Sergeant

doi:10.14814/phy2.12520

Audrey Wallace, Deborah Gabriel + Show 4 more

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https://doi.org/10.14814/phy2.12520

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Journal: Physiological Reports	Publication Date: Sep 1, 2015
Citations: 20	License type: cc-by

Affiliation: Dundalk Institute of Technology

Abstract

Stimulation of intramural nerves in the vas deferens of many species yields a classical biphasic contraction comprised of an initial fast component, mediated by P2X receptors and a second slower component, mediated by α1-adrenoceptors. It is also recognized that sympathetic nerve-mediated contractions of the vas deferens can be modulated by acetylcholine (Ach), however there is considerable disagreement in the literature regarding the precise contribution of cholinergic nerves to contraction of the vas deferens. In this study we examined the effect of cholinergic modulators on electric field stimulation (EFS)-evoked contractions of rabbit vas deferens and on cytosolic Ca2+ levels in isolated vas deferens smooth muscle cells (VDSMC). The sustained component of EFS-evoked contractions was inhibited by atropine and by the selective M3R antagonist, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP). EFS-evoked contractions were potentiated by Ach, carbachol (Cch), and neostigmine. The sustained phase of the EFS-evoked contraction was inhibited by prazosin, an α1-adrenoceptor antagonist and guanethidine, an inhibitor of noradrenaline release, even in the continued presence of Ach, Cch or neostigmine. The soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one enhanced the amplitude of EFS-evoked contractions and reduced the inhibitory effects of 4-DAMP. Isolated VDSMC displayed spontaneous Ca2+ oscillations, but did not respond to Cch. However, the α1-adrenoceptor agonist, phenylephrine, evoked a Ca2+ transient and contracted the cells. These data suggest that EFS-evoked contractions of the rabbit vas deferens are potentiated by activation of M3 receptors and reduced by activation of a sGC-dependent inhibitory pathway.

Highlights

Contraction of the vas deferens is responsible for the movement of sperm from the epididymis to the urethra and its dysfunction is associated with the occurrence of several ejaculatory disorders, including premature ejaculation (Michel 2007; Burnstock 2009; Buvat 2011)
Stimulation of sympathetic nerves in the vas deferens leads to a classical biphasic contractile response, composed of an initial transient contraction, sometimes referred to as a “twitch” contraction followed by a secondary sustained contraction, known as the “hump” contraction
Atropine had little effect on the transient component, but abolished the sustained, second component of the contraction. This effect was consistent in six preparations where the mean amplitude of the second component of contraction was reduced from 10.4 Æ 5.1 to 0.14 Æ 0.04 mN (P < 0.05) and the transient contraction was not affected by the drug (15.24 Æ 6.3 mN under control conditions vs. 15.15 Æ 5.9 mN in atropine, P > 0.05)

Summary

Introduction

Contraction of the vas deferens is responsible for the movement of sperm from the epididymis to the urethra and its dysfunction is associated with the occurrence of several ejaculatory disorders, including premature ejaculation (Michel 2007; Burnstock 2009; Buvat 2011). The vas deferens contains a rich population of cholinergic nerves (Furness and Iwayama 1972; Gosling and Dixon 1972; Majcen 1984), their precise role and contribution to the biphasic contractions described above remains unclear (Koslov and Andersson 2013). This is partly due to conflicting reports in the a 2015 The Authors.

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