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

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 ␣ 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.

Contractions of the Mouse Prostate Elicited by Acetylcholine Are Mediated by M3 Muscarinic Receptors

“…The decrease in the potency of acetylcholine observed in prostates taken from M 3 muscarinic receptor heterozygous mice may be a product of fewer M 3 muscarinic receptors being available, whereas the response to acetylcholine in prostates taken from M3R(ϩ/ϩ) mice was comparable with our previous results (White et al, 2010). The absence of a contractile response to acetylcholine, except at high concentrations (as discussed previously) in M3R(Ϫ/Ϫ) mice, further confirms the M 3 muscarinic receptor as the subtype mediating contraction in the mouse prostate gland.…”

“…However, this seems unlikely in the prostate because the residual contractile response to electrical-field stimulation in prostates taken from M3R(Ϫ/Ϫ) mice is abolished by the ␣ 1 -adrenoceptor antagonist prazosin. Furthermore this confirms that the nerve-mediated contractile response in the mouse prostate is mediated by both muscarinic receptors and ␣ 1L -adrenoceptors (White et al, 2010).…”

“…In the prostate gland, cholinergic innervation acting at muscarinic receptors in the glandular epithelium is thought to be responsible primarily for the secretion of prostatic fluids (Ventura et al, 2002). However, in the mouse prostate gland, in addition to noradrenaline acting at ␣ 1L -adrenoceptors (Gray and Ventura, 2006), we have shown a significant cholinergic component of the nerve-mediated contractile response whereby acetylcholine acts at muscarinic receptors to mediate contraction (White et al, 2010). Currently, the muscarinic receptor subtype mediating the contractile response in the mouse prostate gland is unknown.…”

Male contraception via simultaneous knockout of α 1A -adrenoceptors and P2X1-purinoceptors in mice

“…Isolated organ bath experiments were conducted as described (25,26). Intracellular electrical recordings of vas deferens smooth muscle were as described (15).…”

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

“…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.…”