Characterization of Muscarinic Cholinoceptor in Primary Culture of Smooth Muscle Cells from Human Prostate

Yazawa, Hidenori; Saita, Yuji; Iida, Emi; Honma, Yumiko; Morita, Takashi; Honda, Kazuo

doi:10.1016/s0022-5347(17)32346-7

Cited by 34 publications

(27 citation statements)

References 19 publications

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“…These results are consistent with findings in the rat prostate, where the M 3 muscarinic receptor subtype mediates contraction (Lau and Pennefather, 1998) and is localized in the stromal tissue (Nadelhaft, 2003). However, this is in contrast to findings in the human (Yazawa et al, 1994) and canine (Ferná ndez et al, 1998) prostates where M 2 muscarinic receptors are thought to mediate contraction and in the guinea pig prostate where M 1 muscarinic receptors facilitate contraction (Lau et al, 2000).…”

Section: Discussionsupporting

confidence: 89%

“…In cultures of human prostatic smooth muscle cells only M 2 , M 3 , and M 4 muscarinic receptor subtype mRNA expression is observed (Obara et al, 2000), with the M 2 muscarinic receptor being the most abundant. In a separate study of human prostatic smooth muscle cell cultures, M 2 muscarinic receptors were observed by radioligand binding experiments and mediated a decrease in cAMP accumulation (Yazawa et al, 1994).…”

Section: Introductionmentioning

confidence: 97%

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

White¹,

Short²,

Haynes³

et al. 2011

J Pharmacol Exp Ther

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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.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 97%

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

White¹,

Short²,

Haynes³

et al. 2011

J Pharmacol Exp Ther

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“…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. 23 Thus, cultured cell evidence is quite consistent with the effects of cholinergic agonists in human prostatic tissue and indicates the potential complexity of signalling in the human prostatic stroma.…”

Section: Cultured Cell Models Of Human Prostate Contractilitymentioning

confidence: 97%

Current models of human prostate contractility

Haynes

Ventura

2005

Clin Exp Pharma Physio

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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.

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“…In fact, mAChR agonist-induced contractions of the ventral lobe of the rat prostate seem to be mediated by M 3 mAChR (Lau andPennefather 1998, Ventura et al 2002). The expression of mAChR subtypes varies among the different lobes of the rat prostate; immunohistochemistry combined with RT-PCR analysis suggests that M 3 mAChRs are predominantly expressed in the ventral lobe and M 2 mAChRs in the dorsolateral lobe (Pontari et al 1998 (Yazawa et al 1994) are detected in cultured prostate smooth muscle cells from human patients with benign prostatic hypertrophy. Additionally, M 1 mAChRs are present on glandular epithelial cells from these patients (Ruggieri et al 1995) and M 3 mAChR is present in the LNCaP prostatic cancer cell line (Rayford et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Expression and function of G-protein-coupled receptorsin the male reproductive tract

Avellar

Lazari

Porto

2009

An. Acad. Bras. Ciênc.

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This review focuses on the expression and function of muscarinic acetylcholine receptors (mAChRs), α 1 -adrenoceptors and relaxin receptors in the male reproductive tract. The localization and differential expression of mAChR and α 1 -adrenoceptor subtypes in specific compartments of the efferent ductules, epididymis, vas deferens, seminal vesicle and prostate of various species indicate a role for these receptors in the modulation of luminal fluid composition and smooth muscle contraction, including effects on male fertility. Furthermore, the activation of mAChRs induces transactivation of the epidermal growth factor receptor (EGFR) and the Sertoli cell proliferation. The relaxin receptors are present in the testis, RXFP1 in elongated spermatids and Sertoli cells from rat, and RXFP2 in Leydig and germ cells from rat and human, suggesting a role for these receptors in the spermatogenic process. The localization of both receptors in the apical portion of epithelial cells and smooth muscle layers of the vas deferens suggests an involvement of these receptors in the contraction and regulation of secretion.

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Characterization of Muscarinic Cholinoceptor in Primary Culture of Smooth Muscle Cells from Human Prostate

Cited by 34 publications

References 19 publications

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

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

Current models of human prostate contractility

Expression and function of G-protein-coupled receptorsin the male reproductive tract

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Characterization of Muscarinic Cholinoceptor in Primary Culture of Smooth Muscle Cells from Human Prostate

Cited by 34 publications

References 19 publications

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

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

Current models of human prostate contractility

Expression and function of G-protein-coupled receptorsin the male reproductive tract

Contact Info

Product

Resources

About

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

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