Pharmacological Characterization of Isolated Human Prostate

Kester, Robert R.; Mooppan, Unni M.M.; Gousse, Angelo E.; Alver, J E; Gintautas, J; Gulmi, Frederick A.; Ar, Amos; Kim, Hong

doi:10.1097/01.ju.0000080440.74266.b1

Cited by 32 publications

(30 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…98 Acetylcholine has been shown to have either no direct contractile effect in human prostatic tissue (although it potentiated responses to exogenous noradrenaline) 9 or to elicit small contractions. 49 These findings are consistent with the work of Yazawa et al, who showed that human cultured prostatic stromal cells contained a modest number of M2 muscarinic receptors coupled, presumably via Gi, to adenylate cyclase. 99 Previously, we have shown that, in non-prostatic smooth muscle, agents that activate Gi-coupled receptors may not necessarily elicit contractions, but may potentiate the contractile responses to other agents.…”

Section: Cultured Cell Models Of Human Prostate Contractilitysupporting

confidence: 92%

“…47,48 The effects of muscarinic agonists in human prostate are equivocal; they have been shown to potentiate responses to noradrenaline, but not to cause contraction, 9 and they have been shown to elicit contractions in their own right. 49 There are many likely scenarios that could explain these findings; the simplest is that most prostatic muscarinic receptors are located on the prostatic epithelium (rather than the stroma). 50 Alternatively, it is possible that, because human epithelial cells possess both muscarinic receptors and nitric oxide synthase, 9,14,51 exogenous acetylcholine could activate epithelial cell nitric oxide synthase to reduce stromal contractility mediated by cholinergic agonists.…”

Section: Animal Prostate Models Of Human Prostate Contractilitymentioning

confidence: 99%

See 1 more Smart Citation

Current models of human prostate contractility

Haynes

Ventura

2005

Clin Exp Pharma Physio

View full text Add to dashboard Cite

SUMMARY1. The human prostate is a compact gland contributing to seminal fluid. With increasing age, most humans will develop benign prostatic hyperplasia, a condition of prostatic enlargement and contractility that leads to occlusion of the urethra. Over many years, investigators have used a variety of animal and cell culture models to elucidate some of the contractile and proliferative mechanisms that may be associated with the development of this condition.2. This review briefly assesses the current state of knowledge of the mechanisms underlying human prostatic contractility and compares it with that of animal and cell culture models. It is not intended as a comprehensive methodological review, nor is it intended to indicate our preferences for either model. Our aim is to correlate findings from animal and cell culture models with the current understanding of human prostate contractility.3. We hope that the present review will increase awareness of the suitability of the current models in developing our understanding of benign prostatic hyperplasia.

show abstract

Section: Cultured Cell Models Of Human Prostate Contractilitysupporting

confidence: 92%

Section: Animal Prostate Models Of Human Prostate Contractilitymentioning

confidence: 99%

Current models of human prostate contractility

Haynes

Ventura

2005

Clin Exp Pharma Physio

View full text Add to dashboard Cite

show abstract

“…Unlike in the mouse prostate, the cholinergic component of nerve-mediated contraction in the human prostate is small compared with the adrenergic response (Caine et al, 1975;Hedlund et al, 1985;Gup et al, 1989;Kester et al, 2003). However, another study has observed an adreno-muscarinic synergy in contraction of the human prostate (Roosen et al, 2009).…”

Section: Discussionmentioning

confidence: 93%

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

White¹,

Short²,

Haynes³

et al. 2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Increased smooth muscle tone in the human prostate contributes to the symptoms associated with benign prostatic hyperplasia. In the mouse prostate gland, cholinergic innervation is responsible for a component of the nerve-mediated contractile response. This study investigates the muscarinic receptor subtype responsible for the cholinergic contractile response in the mouse prostate gland. To characterize the muscarinic receptor subtype, mouse prostates taken from wild-type or M 3 muscarinic receptor knockout mice were mounted in organ baths. The isometric force that tissues developed in response to electricalfield stimulation or exogenously applied cholinergic agonists in the presence or absence of a range of muscarinic receptor antagonists was evaluated. Carbachol elicited reproducible and concentration-dependent contractions of the isolated mouse prostate, which were antagonized by the presence of muscarinic receptor antagonists. Calculation of antagonist affinities (pA 2 values) indicated a rank order of antagonist potencies in the mouse prostate of: darifenacin (9.08) ϭ atropine (9.07) ϭ 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (9.02) Ͼ cyclohexyl-hydroxy-phenyl-(3-piperidin-1-ylpropyl)silane (7.85) Ͼ cyclohexyl-(4-fluorophenyl)-hydroxy-(3-piperidin-1-ylpropyl)silane (7.39) Ͼ himbacine (7.19) Ͼ pirenzipine (6.88) Ͼ methoctramine (6.20). Furthermore, genetic deletion of the M 3 muscarinic receptor inhibited prostatic contractions to electrical-field stimulation or exogenous administration of acetylcholine. In this study we identified that the cholinergic component of contraction in the mouse prostate is mediated by the M 3 muscarinic receptor subtype. Pharmacological antagonism of the M 3 muscarinic receptor may be a beneficial additional target for the treatment of benign prostatic hyperplasia in the human prostate gland.

show abstract

“…Some studies have also reported that muscarinic receptor agonists mediate contraction in the human prostate (Caine et al, 1975;Gup et al, 1989;Kester et al, 2003), whereas in other human studies no contraction was observed (Hedlund et al, 1985). When observed, cholinergic receptor agonist-mediated contraction seems to be localized to the prostatic capsule.…”

Section: Discussionmentioning

confidence: 94%

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

White

Short

Haynes

et al. 2010

J Pharmacol Exp Ther

View full text Add to dashboard Cite

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.

show abstract

Pharmacological Characterization of Isolated Human Prostate

Cited by 32 publications

References 21 publications

Current models of human prostate contractility

Current models of human prostate contractility

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

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

Contact Info

Product

Resources

About

Pharmacological Characterization of Isolated Human Prostate

Cited by 32 publications

References 21 publications

Current models of human prostate contractility

Current models of human prostate contractility

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

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

Contact Info

Product

Resources

About

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