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 α1-adrenoceptor antagonists as pharmacotherapies for benign prostatic hyperplasia. Previous studies in mice have demonstrated that a residual nonadrenergic component to nerve stimulation remains after α1-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, α1A-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, α1A-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 α1A-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.
Footnotes
-
This work was supported by the ANZ Trustees [Grant 09/3164] (to S.V.), the National Health and Medical Research Council (Australia) [Grant 334136] (to S.V.), and the Wellcome Trust [Grant 080487/Z/06/Z] (to R.J.E.) for the generation of the P2X1 purinoceptor knockout mouse.
-
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.110.172130.
-
ABBREVIATIONS:
- BPH
- benign prostatic hyperplasia
- ANOVA
- analysis of variance
- KO
- knockout.
- Received June 28, 2010.
- Accepted August 18, 2010.
- Copyright © 2010 by the American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|