Receptors mediating contraction of isolated human vas deferens

Canevari, A.; Pacifico, P.; Cugurra, F; C, Giglio; Nadalini, V. F.

doi:10.1016/0031-6989(86)90130-x

Cited by 5 publications

(3 citation statements)

References 25 publications

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“…Human VD and prostate [143,144] ATP Not available (NA) NA Excitatory Rat and guinea pig VD and prostate gland [145][146][147] Human VD [110] Dopamine Excitatory Rats [64,148] Humans [62] Excitatory Human VD and prostate [149,150] Glutamic acid (glutamate)…”

Section: Norepinepherine Excitatorymentioning

confidence: 99%

Premature ejaculation: focus on therapeutic targets

Abdel‐Hamid

Jannini

Andersson

2009

Expert Opinion on Therapeutic Targets

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Background : Premature ejaculation (PE) is poorly defined but the most common male sexual complaint. It can be treated with strategies including oral pharmacotherapy, topical anaesthetics, behavioural therapy and surgery. Although PE is treatable in most, but not all, patients by currently available modalities, long term success rates have been disappointing. An approved treatment so far does not exist. Objective : To review literature on the current and potential therapeutic targets for PE. Methods : Available English-language published literature is reviewed. Results/conclusions : There are many targets for future therapeutic approaches to PE that may address the shortcomings of existing therapy. Selecting the best targets depends heavily on their playing a prominent role in PE. Exploiting the full therapeutic potential of these targets will require additional basic and clinical research.

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Section: Norepinepherine Excitatorymentioning

confidence: 99%

Premature ejaculation: focus on therapeutic targets

Abdel‐Hamid

Jannini

Andersson

2009

Expert Opinion on Therapeutic Targets

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“…Similarly, Canevari et al. (1986) reported that exogenous application of cholinergic drugs to human vas deferens were totally inactive, whereas Miranda et al. (1992) found that exogenous application of acetylcholine (Ach)-induced concentration-dependent contractions.…”

Section: Introductionmentioning

confidence: 99%

“…For example, some studies showed that electric field stimulation (EFS)-evoked contractions of the vas deferens were inhibited by the muscarinic receptor (MR) antagonist atropine (Fukushi and Wakui 1986;White et al 2010) whereas as others showed that atropine had little, or no effect (Nakanishi et al 2004;Cuprian et al 2005). Similarly, Canevari et al (1986) reported that exogenous application of cholinergic drugs to human vas deferens were totally inactive, whereas Miranda et al (1992) found that exogenous application of acetylcholine (Ach)-induced concentration-dependent contractions.…”

Section: Introductionmentioning

confidence: 99%

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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Opioid receptor characterisation of neuronally stimulated isolated human vas deferens

Root

Wakenhut

Siggins

et al. 2012

Naunyn-Schmiedeberg's Arch Pharmacol

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Rodent vas deferens is routinely used as a native tissue preparation to assess opioid pharmacology of new compounds. The aim of this study was to investigate the effects of a selected number of opioid compounds in the human vas deferens. Stable contractions to electrical field stimulation (EFS) were inhibited by guanethidine (1 μM) and tetrodotoxin (TTX, 1 μΜ), confirming neuronally induced contractions. Contractile responses to EFS were inhibited by the selective δ-opioid agonists (DPDPE ([D-Pen2,5]enkephalin), PF-391459 (3-{4-[(R)-[(2S,5R)-4-benzyl-2,5-dimethylpiperazin-1-yl](3-hydroxyphenyl)methyl]phenyl}propanoic acid) and SNC-80 ((+)-4-[(αR)-α-((2 S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide)) (tested from 1 ρM to 10 μM or maximum), and the μ-opioid agonists DAMGO ([D-Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin), loperamide and SC-50484 (N-{2-[(N-acetyl-L-phenylalanyl)amino]-1,1-dimethylethyl}-L-tyrosinamide). There was no effect using the selective κ agonist U50488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide) (tested from 1 ρM to 10 μM). The selective δ-opioid antagonist naltrindole (10 nM) surmountably antagonised the responses to DPDPE, but not to PF-3911459. Responses to DAMGO were completely abolished in the presence of the μ-opioid antagonist CTAP (3 μM), which only weakly antagonised responses to SC-50484. We conclude that under these conditions, δ and μ-opioid receptors, but not κ-opioid receptors, are functional in the neuronally stimulated longitudinal human vas deferens. Additionally, the human vas deferens preparation can be used as part of a drug discovery screening project to assess opioid potency, efficacy and selectivity at native human tissues, thus providing more confidence in translation.

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Receptors mediating contraction of isolated human vas deferens

Cited by 5 publications

References 25 publications

Premature ejaculation: focus on therapeutic targets

Premature ejaculation: focus on therapeutic targets

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

Opioid receptor characterisation of neuronally stimulated isolated human vas deferens

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