Cholinergic innervation of the mouse isolated vas deferens

Cuprian, Alina; Solanki, Pravesh; Jackson, Margaret; Cunnane, T.C.

doi:10.1038/sj.bjp.0706357

Cited by 16 publications

(18 citation statements)

References 21 publications

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“…Acetylcholine has also been shown to enhance noradrenalinemediated contraction in the human prostate (Roosen et al, 2009), indicating a possible synergism. It has been shown that there are functional muscarinic receptors mediating contraction in vasa deferentia taken from the mouse (Cuprian et al, 2005) and guinea pig (Solanki et al, 2007), and we also observed that atropine attenuated contraction in vasa deferentia taken from wild-type mice. However, after purinergic and adrenergic blockade we did not observe a cholinergic residual response.…”

Section: Discussionsupporting

confidence: 74%

The Residual Nonadrenergic Contractile Response to Nerve Stimulation of the Mouse Prostate Is Mediated by Acetylcholine but Not ATP in a Comparison with the Mouse Vas Deferens

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Haynes

et al. 2010

J Pharmacol Exp Ther

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Neuronal release of noradrenaline is primarily responsible for the contraction of prostatic smooth muscle in all species, and this forms the basis for the use of ␣ 1 -adrenoceptor antagonists as pharmacotherapies for benign prostatic hyperplasia. Previous studies in mice have demonstrated that a residual nonadrenergic component to nerve stimulation remains after ␣ 1 -adrenoceptor antagonism. In the guinea pig and rat prostate and the vas deferens of guinea pigs, rats, and mice, ATP is the mediator of this residual contraction. This study investigates the mediator of residual contraction in the mouse prostate. Whole prostates from wild-type, ␣ 1A -adrenoceptor, and P2X1-purinoceptor knockout mice were mounted in organ baths, and the isometric force that tissues developed in response to electrical field stimulation or exogenously applied agonists was recorded. Deletion of the P2X1 purinoceptor did not affect nerve-mediated contraction. Furthermore, the P2-purinoceptor antagonist suramin (30 M) failed to attenuate nerve-mediated contractions in wild-type, ␣ 1A -adrenoceptor, or P2X1-purinoceptor knockout mice. Atropine (1 M) attenuated contraction in prostates taken from wild-type mice. In the presence of prazosin (0.3 M) or guanethidine (10 M), or in prostates taken from ␣ 1A -adrenoceptor knockout mice, residual nerve-mediated contraction was abolished by atropine (1 M), but not suramin (30 M). Exogenously administered acetylcholine elicited reproducible concentration-dependent contractions of the mouse prostate that were atropine-sensitive (1 M), but not prazosin-sensitive (0.3 M). Acetylcholine, but not ATP, mediates the nonadrenergic component of contraction in the mouse prostate. This cholinergic component of prostatic contraction is mediated by activation of muscarinic receptors.

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Section: Discussionsupporting

confidence: 74%

The Residual Nonadrenergic Contractile Response to Nerve Stimulation of the Mouse Prostate Is Mediated by Acetylcholine but Not ATP in a Comparison with the Mouse Vas Deferens

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Short

Haynes

et al. 2010

J Pharmacol Exp Ther

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“…In mouse vas deferens, contraction and confocal studies have shown that nicotine increases the amplitude of the bretylium-resistant contraction (Cuprian et al 2005) and spontaneous Ca 2+ transients in all varicosities, located on either bretylium-sensitive or bretylium-resistant nerve terminals (Brain et al 2001; Jackson et al 2001; Jackson and Cunnane 2002). These nerve terminals were considered to be preterminal sympathetic fibres, sensory nerves or cholinergic nerves.…”

Section: Discussionmentioning

confidence: 99%

“…We have recently reported a cholinergic component of contraction in the mouse vas deferens which is limited by the action of acetylcholinesterase (AChE), enhanced by nicotine and blocked by muscarinic acetylcholine receptor (mAChR) antagonists (Cuprian et al 2005). Nicotine acts at prejunctional nicotinic acetylcholine receptors (nAChRs) and therefore increases neurotransmitter release.…”

Section: Introductionmentioning

confidence: 99%

Cholinergic innervation of the guinea-pig isolated vas deferens

Solanki

Cuprian-Beltechi

Cunnane

2007

Naunyn-Schmied Arch Pharmacol

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Recently, a cholinergic neurogenic component of contraction has been characterised in the aganglionic mouse vas deferens. In this paper, a cholinergic component of contraction in the guinea-pig vas deferens is characterised pharmacologically. A residual, tetrodotoxin-sensitive (TTX, 0.3 microM), neurogenic contraction was revealed after prolonged exposure (5 h) to the adrenergic neurone blocker bretylium (20 microM) or in the presence of prazosin (100 nM) and alpha,beta-methylene ATP (1 microM), a purinergic agonist which desensitizes P2X receptors. The bretylium-resistant component was potentiated by the acetylcholinesterase (AChE) inhibitor neostigmine (10 microM) and inhibited by the muscarinic-receptor (mAChR) antagonist cyclopentolate (1 microM). Nicotine (30 microM) enhanced the bretylium-resistant component. Neostigmine increased the second component of contraction in the presence of prazosin and alpha,beta-methylene ATP, whilst yohimbine (1 microM), an alpha(2) adrenergic receptor antagonist, enhanced both the first and second components of the electrically evoked contraction. These enhanced contractions were blocked by cyclopentolate in both cases. Nicotine enhanced the cholinergic component of contraction revealed by neostigmine but failed to have any detectable effects in the presence of cyclopentolate. Neostigmine alone increased the slow component of contraction which was reversed by cyclopentolate to control levels. The M(3) receptor-antagonist 4-DAMP (10 nM) markedly inhibited the cholinergic component of contraction to a level comparable with cyclopentolate. Laser microscopy has shown that neostigmine also increased the frequency of spontaneous Ca(2+) transients remaining in smooth muscle cells after perfusion with prazosin and alpha,beta-methylene ATP, an effect blocked by 4-DAMP. These experimental data show that there is a functional cholinergic innervation in the guinea-pig vas deferens whose action is limited by acetylcholinesterase, blocked by cyclopentolate and mediated through M3 receptors. Moreover, by blocking the cholinesterase, the increased amount of ACh generates spontaneous Ca(2+) transients in smooth muscle cells.

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“…However, although a direct cholinergic innervation has been reported in murine vas deferens (Cuprian et al. 2005) it seems unlikely to account for the results of this study, for two main reasons. Firstly exogenous application of Cch failed to evoke a response in isolated VDSMC and secondly, we found that both prazosin and guanethidine inhibited the sustained phase of EFS-evoked contractions.…”

Section: Discussionmentioning

confidence: 74%

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

et al. 2015

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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.

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Cholinergic innervation of the mouse isolated vas deferens

Cited by 16 publications

References 21 publications

The Residual Nonadrenergic Contractile Response to Nerve Stimulation of the Mouse Prostate Is Mediated by Acetylcholine but Not ATP in a Comparison with the Mouse Vas Deferens

The Residual Nonadrenergic Contractile Response to Nerve Stimulation of the Mouse Prostate Is Mediated by Acetylcholine but Not ATP in a Comparison with the Mouse Vas Deferens

Cholinergic innervation of the guinea-pig isolated vas deferens

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

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