Endothelin receptors and their cellular signal transduction mechanism in human cultured prostatic smooth muscle cells

Saita, Yuji; Koizumi, Tomonobu; Yazawa, Hidenori; Morita, Takashi; Takenaka, Toichi; Honda, Kazuo

doi:10.1038/sj.bjp.0701179

Cited by 9 publications

(11 citation statements)

References 35 publications

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“…These mRNA expression data support the pharmacological analysis, as found for human ciliary [29] and human prostate smooth muscle [30]. These mRNA expression data support the pharmacological analysis, as found for human ciliary [29] and human prostate smooth muscle [30].…”

Section: Discussionsupporting

confidence: 86%

Pharmacological and molecular biological evidence for ETA endothelin receptor subtype mediating mechanical responses in the detrusor smooth muscle of the human urinary bladder

et al. 1999

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A B S T R A C TThe aim of this study was to characterize endothelin receptor subtypes of the detrusor muscle of the human urinary bladder. The receptor subtypes mediating endothelin (ET)-1-induced activity in the human detrusor smooth muscles have been characterized using isometric contraction and reverse transcription-polymerase chain reaction (RT-PCR). ET-1 (a nonselective ET receptor agonist ; 10 − 10 M to 10 − 6 M) exhibited concentration-dependent contractions in human urinary bladder with a plateau at concentrations above 3i10 − 7 M. Neither IRL1620 nor sarafotoxin S6c (both ET B -selective agonists ; 10 − 10 M to 10 − 6 M) elicited contractile activity in the human urinary bladder detrusor smooth muscle. FR139317 (an ET A -selective antagonist ; 10 − 7 M to 10 − 5 M) produced a marked shift to the right of the ET-1 concentrationresponse curve in human urinary bladder detrusor smooth muscle (from the Schild plot TpA 2 l 7.96 ; slope l 0.95). In contrast, RES701-1 (an ET B -selective antagonist ; 10 − 7 M to 10 − 5 M) had no effect on the ET-1 concentration-response curve. RT-PCR revealed positive amplification of ET A receptor mRNA fragment, but not ET B . These results indicate that the ET-1-induced contractile effects of urinary bladder detrusor smooth muscle seem to be mediated mainly by the ET A receptor, not by the ET B receptor.

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Section: Discussionsupporting

confidence: 86%

Pharmacological and molecular biological evidence for ETA endothelin receptor subtype mediating mechanical responses in the detrusor smooth muscle of the human urinary bladder

et al. 1999

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“…On the other hand, ET-1 has been reported to be one of the agents that cause the contraction of the human prostate. 12,13 Therefore, in the present study we used ET-1 as an alternate contractile agonist in the CHPSCs ring experiments. As shown in Figure 1, ROCK inhibitor decreased the sustained contraction induced by ET-1.…”

Section: Discussionmentioning

confidence: 99%

RhoA/Rho kinase‐mediated Ca²⁺ sensitization in the contraction of human prostate

Takahashi

Nishimura

Seki

et al. 2007

Neurourology and Urodynamics

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“…In vitro, isolated human prostates were contracted by ET-1, and the contractions were found to be calcium dependent and dihydropyridine and ·-adrenoceptor antagonist insensitive Thiyagarajan [37]. These results suggest that endothelins mayplay a functional role in BPH [38,39]. ET-1 and ET-2 were also found to induce DNA synthesis and cell growth.…”

Section: Endothelin Receptorsmentioning

confidence: 76%

α-Adrenoceptor Antagonists in the Treatment of Benign Prostate Hyperplasia

Thiyagarajan

2002

Pharmacology

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Benign prostate hyperplasia (BPH) is a common malady affecting elderly men throughout the world, and it is the most common cause of voiding dysfunctions in man. The disease becomes prevalent, as the mean age of the population increases. In BPH the glandular cells and myofibroblasts of periurethral and transition zones proliferate excessively. This excessive growth of tissue mass physically compresses the urethra, leading to urinary obstruction and lower urinary tract symptoms (LUTS). Another major factor that contributes to LUTS in BPH is the increase in smooth muscle tone, a dynamic component. Contraction of the prostate gland is mainly under the control of the autonomic system and is mediated through α-adrenoceptors. In addition to α₁-adrenoceptors, there are many other components that influence growth and contraction of the prostate gland, resulting in the development of BPH and LUTS. The prostate gland is contracted on stimulating 5-HT, endothelin, tachykinin, and muscarinic cholinergic receptors. Growth of the prostate gland is under the control of androgens, endothelin growth factor, vasoactive intestinal peptide, nerve growth factor, and growth hormone. The combination of excessive growth and the tone produced by different components results in LUTS and BPH. α₁-Adrenoceptor antagonists were successfully used in the treatment of BPH to relieve the LUTS. The high selectivity of α_1A-adrenoceptor antagonists reflects the uroselectivity. The uroselective compounds like terazosin, doxazosin, tamsulosin, and alfuzosin are in clinical use. Other new potent uroselective compounds, which are analogs of nigulidipine, 5-methyl-urapidil, or naftopidil, are in clinical trials. In addition to α-antagonists, antiandrogens (5α-reductase inhibitors) and polyherbal formulations are used to treat BPH. The success of BPH treatment lies in the development of new chemical entities which are efficacious as well as more uroselective and hence have least side effects.

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Endothelin receptors and their cellular signal transduction mechanism in human cultured prostatic smooth muscle cells

Abstract: 1 Endothelin (ET) receptors, and their cellular signal transduction mechanism, were characterized in a primary culture of human prostatic smooth muscle cells (HP cell

Cited by 9 publications

References 35 publications

Pharmacological and molecular biological evidence for ETA endothelin receptor subtype mediating mechanical responses in the detrusor smooth muscle of the human urinary bladder

Pharmacological and molecular biological evidence for ETA endothelin receptor subtype mediating mechanical responses in the detrusor smooth muscle of the human urinary bladder

RhoA/Rho kinase‐mediated Ca²⁺ sensitization in the contraction of human prostate

α-Adrenoceptor Antagonists in the Treatment of Benign Prostate Hyperplasia

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Endothelin receptors and their cellular signal transduction mechanism in human cultured prostatic smooth muscle cells

Abstract: 1 Endothelin (ET) receptors, and their cellular signal transduction mechanism, were characterized in a primary culture of human prostatic smooth muscle cells (HP cell

Cited by 9 publications

References 35 publications

Pharmacological and molecular biological evidence for ETA endothelin receptor subtype mediating mechanical responses in the detrusor smooth muscle of the human urinary bladder

Pharmacological and molecular biological evidence for ETA endothelin receptor subtype mediating mechanical responses in the detrusor smooth muscle of the human urinary bladder

RhoA/Rho kinase‐mediated Ca2+ sensitization in the contraction of human prostate

α-Adrenoceptor Antagonists in the Treatment of Benign Prostate Hyperplasia

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RhoA/Rho kinase‐mediated Ca²⁺ sensitization in the contraction of human prostate