The functional role of beta-adrenoceptor subtypes in mediating relaxation of pig urethral smooth muscle

Tomonori Yamanishi, Christopher R. Chapple, Kosaku Yasuda, Ken Ichiro Yoshida, Russell Chess-Williams

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Abstract

Purpose: The predominant β-adrenoceptor subtype present in the bladder and urethra is β3-adrenoceptors. We investigated the role of β-adrenoceptors in mediating relaxation of the in vitro female pig urethra. Materials and Methods: Circular strips of urethral tissues were pre-contracted with KCl. Concentration-relaxation curves (CRCs) to β-adrenoceptor agonists were obtained in the absence and presence of antagonists. Results: The nonselective β-agonist isoproterenol in 30 animals and the β3-adrenoceptor agonist BRL37344 in 4 relaxed with high potency (pEC50 7.2 and 8.1, respectively), while the β2-adrenoceptor agonist salbutamol in 6 had low potency (pEC50 6.1). Mean maximal relaxation responses of BRL37344 and salbutamol relative to maximal isoproterenol responses were 89.8% and 76.7%, respectively. Propranolol (10 to 100 nM) in 18 animals antagonized CRCs to isoproterenol with high affinity (apparent pKB 8.6) but the Schild plot had a slope that was significantly less than unity (0.68, p <0.01). High concentrations of the β1-antagonist CGP20712A (3 to 30 μM) in 12 animals had no effect on responses to isoproterenol. The β2-antagonist ICI118551 (30 to 300 nM) in 25 animals antagonized responses to isoproterenol with high affinity (apparent pK B 8.03) with a Schild slope not different from unity (0.79). The β3-antagonist SR59230A (10 to 100 nM) in 12 animals antagonized CRCs to isoproterenol with an apparent pKB of 7 and with a Schild slope that was again significantly less than unity (0.62, p <0.01), indicating that responses to isoproterenol are mediated by more than 1 β-adrenoceptor subtype. According to the Schild plot of unity ICI118551 (3 to 30 nM) in 18 animals competitively antagonized responses to salbutamol with high affinity (pA2 8.5). Conclusions: In the pig urethra β-adrenoceptor mediated relaxations to isoproterenol are mediated via β2 and β3-adrenoceptors, while responses to β 2-adrenoceptor agonists such as salbutamol appear to be mediated only via β2-adrenoceptors.

Original languageEnglish
Pages (from-to)2508-2511
Number of pages4
JournalJournal of Urology
Volume170
Issue number6 I
DOIs
Publication statusPublished - Dec 2003
Externally publishedYes

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Adrenergic Receptors
Smooth Muscle
Swine
Isoproterenol
Albuterol
Urethra
Propranolol
Urinary Bladder

Cite this

Yamanishi, Tomonori ; Chapple, Christopher R. ; Yasuda, Kosaku ; Yoshida, Ken Ichiro ; Chess-Williams, Russell. / The functional role of beta-adrenoceptor subtypes in mediating relaxation of pig urethral smooth muscle. In: Journal of Urology. 2003 ; Vol. 170, No. 6 I. pp. 2508-2511.
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title = "The functional role of beta-adrenoceptor subtypes in mediating relaxation of pig urethral smooth muscle",
abstract = "Purpose: The predominant β-adrenoceptor subtype present in the bladder and urethra is β3-adrenoceptors. We investigated the role of β-adrenoceptors in mediating relaxation of the in vitro female pig urethra. Materials and Methods: Circular strips of urethral tissues were pre-contracted with KCl. Concentration-relaxation curves (CRCs) to β-adrenoceptor agonists were obtained in the absence and presence of antagonists. Results: The nonselective β-agonist isoproterenol in 30 animals and the β3-adrenoceptor agonist BRL37344 in 4 relaxed with high potency (pEC50 7.2 and 8.1, respectively), while the β2-adrenoceptor agonist salbutamol in 6 had low potency (pEC50 6.1). Mean maximal relaxation responses of BRL37344 and salbutamol relative to maximal isoproterenol responses were 89.8{\%} and 76.7{\%}, respectively. Propranolol (10 to 100 nM) in 18 animals antagonized CRCs to isoproterenol with high affinity (apparent pKB 8.6) but the Schild plot had a slope that was significantly less than unity (0.68, p <0.01). High concentrations of the β1-antagonist CGP20712A (3 to 30 μM) in 12 animals had no effect on responses to isoproterenol. The β2-antagonist ICI118551 (30 to 300 nM) in 25 animals antagonized responses to isoproterenol with high affinity (apparent pK B 8.03) with a Schild slope not different from unity (0.79). The β3-antagonist SR59230A (10 to 100 nM) in 12 animals antagonized CRCs to isoproterenol with an apparent pKB of 7 and with a Schild slope that was again significantly less than unity (0.62, p <0.01), indicating that responses to isoproterenol are mediated by more than 1 β-adrenoceptor subtype. According to the Schild plot of unity ICI118551 (3 to 30 nM) in 18 animals competitively antagonized responses to salbutamol with high affinity (pA2 8.5). Conclusions: In the pig urethra β-adrenoceptor mediated relaxations to isoproterenol are mediated via β2 and β3-adrenoceptors, while responses to β 2-adrenoceptor agonists such as salbutamol appear to be mediated only via β2-adrenoceptors.",
author = "Tomonori Yamanishi and Chapple, {Christopher R.} and Kosaku Yasuda and Yoshida, {Ken Ichiro} and Russell Chess-Williams",
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The functional role of beta-adrenoceptor subtypes in mediating relaxation of pig urethral smooth muscle. / Yamanishi, Tomonori; Chapple, Christopher R.; Yasuda, Kosaku; Yoshida, Ken Ichiro; Chess-Williams, Russell.

In: Journal of Urology, Vol. 170, No. 6 I, 12.2003, p. 2508-2511.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The functional role of beta-adrenoceptor subtypes in mediating relaxation of pig urethral smooth muscle

AU - Yamanishi, Tomonori

AU - Chapple, Christopher R.

AU - Yasuda, Kosaku

AU - Yoshida, Ken Ichiro

AU - Chess-Williams, Russell

PY - 2003/12

Y1 - 2003/12

N2 - Purpose: The predominant β-adrenoceptor subtype present in the bladder and urethra is β3-adrenoceptors. We investigated the role of β-adrenoceptors in mediating relaxation of the in vitro female pig urethra. Materials and Methods: Circular strips of urethral tissues were pre-contracted with KCl. Concentration-relaxation curves (CRCs) to β-adrenoceptor agonists were obtained in the absence and presence of antagonists. Results: The nonselective β-agonist isoproterenol in 30 animals and the β3-adrenoceptor agonist BRL37344 in 4 relaxed with high potency (pEC50 7.2 and 8.1, respectively), while the β2-adrenoceptor agonist salbutamol in 6 had low potency (pEC50 6.1). Mean maximal relaxation responses of BRL37344 and salbutamol relative to maximal isoproterenol responses were 89.8% and 76.7%, respectively. Propranolol (10 to 100 nM) in 18 animals antagonized CRCs to isoproterenol with high affinity (apparent pKB 8.6) but the Schild plot had a slope that was significantly less than unity (0.68, p <0.01). High concentrations of the β1-antagonist CGP20712A (3 to 30 μM) in 12 animals had no effect on responses to isoproterenol. The β2-antagonist ICI118551 (30 to 300 nM) in 25 animals antagonized responses to isoproterenol with high affinity (apparent pK B 8.03) with a Schild slope not different from unity (0.79). The β3-antagonist SR59230A (10 to 100 nM) in 12 animals antagonized CRCs to isoproterenol with an apparent pKB of 7 and with a Schild slope that was again significantly less than unity (0.62, p <0.01), indicating that responses to isoproterenol are mediated by more than 1 β-adrenoceptor subtype. According to the Schild plot of unity ICI118551 (3 to 30 nM) in 18 animals competitively antagonized responses to salbutamol with high affinity (pA2 8.5). Conclusions: In the pig urethra β-adrenoceptor mediated relaxations to isoproterenol are mediated via β2 and β3-adrenoceptors, while responses to β 2-adrenoceptor agonists such as salbutamol appear to be mediated only via β2-adrenoceptors.

AB - Purpose: The predominant β-adrenoceptor subtype present in the bladder and urethra is β3-adrenoceptors. We investigated the role of β-adrenoceptors in mediating relaxation of the in vitro female pig urethra. Materials and Methods: Circular strips of urethral tissues were pre-contracted with KCl. Concentration-relaxation curves (CRCs) to β-adrenoceptor agonists were obtained in the absence and presence of antagonists. Results: The nonselective β-agonist isoproterenol in 30 animals and the β3-adrenoceptor agonist BRL37344 in 4 relaxed with high potency (pEC50 7.2 and 8.1, respectively), while the β2-adrenoceptor agonist salbutamol in 6 had low potency (pEC50 6.1). Mean maximal relaxation responses of BRL37344 and salbutamol relative to maximal isoproterenol responses were 89.8% and 76.7%, respectively. Propranolol (10 to 100 nM) in 18 animals antagonized CRCs to isoproterenol with high affinity (apparent pKB 8.6) but the Schild plot had a slope that was significantly less than unity (0.68, p <0.01). High concentrations of the β1-antagonist CGP20712A (3 to 30 μM) in 12 animals had no effect on responses to isoproterenol. The β2-antagonist ICI118551 (30 to 300 nM) in 25 animals antagonized responses to isoproterenol with high affinity (apparent pK B 8.03) with a Schild slope not different from unity (0.79). The β3-antagonist SR59230A (10 to 100 nM) in 12 animals antagonized CRCs to isoproterenol with an apparent pKB of 7 and with a Schild slope that was again significantly less than unity (0.62, p <0.01), indicating that responses to isoproterenol are mediated by more than 1 β-adrenoceptor subtype. According to the Schild plot of unity ICI118551 (3 to 30 nM) in 18 animals competitively antagonized responses to salbutamol with high affinity (pA2 8.5). Conclusions: In the pig urethra β-adrenoceptor mediated relaxations to isoproterenol are mediated via β2 and β3-adrenoceptors, while responses to β 2-adrenoceptor agonists such as salbutamol appear to be mediated only via β2-adrenoceptors.

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DO - 10.1097/01.ju.0000085596.11247.78

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SP - 2508

EP - 2511

JO - Journal of Urology

JF - Journal of Urology

SN - 0022-5347

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