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J Pharmacol Exp Ther. 2010 Nov;335(2):489-96. doi: 10.1124/jpet.110.172130. Epub 2010 Aug 19.

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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  • 1Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.

Abstract

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 α(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 α(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, α(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 μM) failed to attenuate nerve-mediated contractions in wild-type, α(1A)-adrenoceptor, or P2X1-purinoceptor knockout mice. Atropine (1 μM) attenuated contraction in prostates taken from wild-type mice. In the presence of prazosin (0.3 μM) or guanethidine (10 μM), or in prostates taken from α(1A)-adrenoceptor knockout mice, residual nerve-mediated contraction was abolished by atropine (1 μM), but not suramin (30 μM). Exogenously administered acetylcholine elicited reproducible concentration-dependent contractions of the mouse prostate that were atropine-sensitive (1 μM), but not prazosin-sensitive (0.3 μM). 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.

PMID:
20724483
PMCID:
PMC2967401
DOI:
10.1124/jpet.110.172130
[PubMed - indexed for MEDLINE]
Free PMC Article
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