The effects of tamsulosin, a high affinity antagonist at functional α(1A)- and α(1D)-adrenoceptor subtypes

A. J. Noble, R. Chess-Williams, C. Couldwell, K. Furukawa, T. Uchyiuma, C. Korstanje, C. R. Chapple

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Abstract

1. The actions of the α1-adrenoceptor antagonist tamsulosin have been examined at functional α1-adrenoceptor subtypes and compared with those at the human prostate receptor. 2. At the α(1D)-adrenoceptors of the rat aorta, tamsulosin acted as a competitive antagonist with a high affinity (pK(B) = 10.1). 3. At the α(1B)-adrenoceptor of the rat spleen and rabbit corpus cavernosum penis, tamsulosin again acted as a competitive antagonist but with a significantly lower affinity (pK(B) = 8.9-9.2). 4. Tamsulosin acted as an unsurmountable antagonist of the α(1A)-adrenoceptor-mediated responses of the rat and human vas deferens, reducing maximal responses to phenylephrine by 20% and 50%, respectively, at an antagonist concentration of 1 nM. Responses of depolarized (100 mM KCl) rat vas deferens preparations were unaffected by 10 nM tamsulosin but this concentration reduced maximal responses to 5-hydroxytryptamine (5-HT) in this tissue. 5. When longer antagonist incubation periods (≤ 60 min) were used, tamsulosin behaved as a competitive antagonist on the human prostate with a significantly higher affinity (pK(B) = 10.0) than obtained at the α(1B)-adrenoceptor. 6. The data demonstrate that tamsulosin is a high affinity antagonist at functional α1-adrenoceptors with a selectivity α(1D) ≤ α(1A) > α(1B). In some tissues the compound exhibits an additional unsurmountable antagonist action, the clinical significance of which is unknown.

Original languageEnglish
Pages (from-to)231-238
Number of pages8
JournalBritish Journal of Pharmacology
Volume120
Issue number2
DOIs
Publication statusPublished - 30 Jan 1997
Externally publishedYes

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tamsulosin
Adrenergic Receptors
Vas Deferens
Prostate
Penis
Phenylephrine
Aorta
Serotonin

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Noble, A. J. ; Chess-Williams, R. ; Couldwell, C. ; Furukawa, K. ; Uchyiuma, T. ; Korstanje, C. ; Chapple, C. R. / The effects of tamsulosin, a high affinity antagonist at functional α(1A)- and α(1D)-adrenoceptor subtypes. In: British Journal of Pharmacology. 1997 ; Vol. 120, No. 2. pp. 231-238.
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abstract = "1. The actions of the α1-adrenoceptor antagonist tamsulosin have been examined at functional α1-adrenoceptor subtypes and compared with those at the human prostate receptor. 2. At the α(1D)-adrenoceptors of the rat aorta, tamsulosin acted as a competitive antagonist with a high affinity (pK(B) = 10.1). 3. At the α(1B)-adrenoceptor of the rat spleen and rabbit corpus cavernosum penis, tamsulosin again acted as a competitive antagonist but with a significantly lower affinity (pK(B) = 8.9-9.2). 4. Tamsulosin acted as an unsurmountable antagonist of the α(1A)-adrenoceptor-mediated responses of the rat and human vas deferens, reducing maximal responses to phenylephrine by 20{\%} and 50{\%}, respectively, at an antagonist concentration of 1 nM. Responses of depolarized (100 mM KCl) rat vas deferens preparations were unaffected by 10 nM tamsulosin but this concentration reduced maximal responses to 5-hydroxytryptamine (5-HT) in this tissue. 5. When longer antagonist incubation periods (≤ 60 min) were used, tamsulosin behaved as a competitive antagonist on the human prostate with a significantly higher affinity (pK(B) = 10.0) than obtained at the α(1B)-adrenoceptor. 6. The data demonstrate that tamsulosin is a high affinity antagonist at functional α1-adrenoceptors with a selectivity α(1D) ≤ α(1A) > α(1B). In some tissues the compound exhibits an additional unsurmountable antagonist action, the clinical significance of which is unknown.",
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The effects of tamsulosin, a high affinity antagonist at functional α(1A)- and α(1D)-adrenoceptor subtypes. / Noble, A. J.; Chess-Williams, R.; Couldwell, C.; Furukawa, K.; Uchyiuma, T.; Korstanje, C.; Chapple, C. R.

In: British Journal of Pharmacology, Vol. 120, No. 2, 30.01.1997, p. 231-238.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - The effects of tamsulosin, a high affinity antagonist at functional α(1A)- and α(1D)-adrenoceptor subtypes

AU - Noble, A. J.

AU - Chess-Williams, R.

AU - Couldwell, C.

AU - Furukawa, K.

AU - Uchyiuma, T.

AU - Korstanje, C.

AU - Chapple, C. R.

PY - 1997/1/30

Y1 - 1997/1/30

N2 - 1. The actions of the α1-adrenoceptor antagonist tamsulosin have been examined at functional α1-adrenoceptor subtypes and compared with those at the human prostate receptor. 2. At the α(1D)-adrenoceptors of the rat aorta, tamsulosin acted as a competitive antagonist with a high affinity (pK(B) = 10.1). 3. At the α(1B)-adrenoceptor of the rat spleen and rabbit corpus cavernosum penis, tamsulosin again acted as a competitive antagonist but with a significantly lower affinity (pK(B) = 8.9-9.2). 4. Tamsulosin acted as an unsurmountable antagonist of the α(1A)-adrenoceptor-mediated responses of the rat and human vas deferens, reducing maximal responses to phenylephrine by 20% and 50%, respectively, at an antagonist concentration of 1 nM. Responses of depolarized (100 mM KCl) rat vas deferens preparations were unaffected by 10 nM tamsulosin but this concentration reduced maximal responses to 5-hydroxytryptamine (5-HT) in this tissue. 5. When longer antagonist incubation periods (≤ 60 min) were used, tamsulosin behaved as a competitive antagonist on the human prostate with a significantly higher affinity (pK(B) = 10.0) than obtained at the α(1B)-adrenoceptor. 6. The data demonstrate that tamsulosin is a high affinity antagonist at functional α1-adrenoceptors with a selectivity α(1D) ≤ α(1A) > α(1B). In some tissues the compound exhibits an additional unsurmountable antagonist action, the clinical significance of which is unknown.

AB - 1. The actions of the α1-adrenoceptor antagonist tamsulosin have been examined at functional α1-adrenoceptor subtypes and compared with those at the human prostate receptor. 2. At the α(1D)-adrenoceptors of the rat aorta, tamsulosin acted as a competitive antagonist with a high affinity (pK(B) = 10.1). 3. At the α(1B)-adrenoceptor of the rat spleen and rabbit corpus cavernosum penis, tamsulosin again acted as a competitive antagonist but with a significantly lower affinity (pK(B) = 8.9-9.2). 4. Tamsulosin acted as an unsurmountable antagonist of the α(1A)-adrenoceptor-mediated responses of the rat and human vas deferens, reducing maximal responses to phenylephrine by 20% and 50%, respectively, at an antagonist concentration of 1 nM. Responses of depolarized (100 mM KCl) rat vas deferens preparations were unaffected by 10 nM tamsulosin but this concentration reduced maximal responses to 5-hydroxytryptamine (5-HT) in this tissue. 5. When longer antagonist incubation periods (≤ 60 min) were used, tamsulosin behaved as a competitive antagonist on the human prostate with a significantly higher affinity (pK(B) = 10.0) than obtained at the α(1B)-adrenoceptor. 6. The data demonstrate that tamsulosin is a high affinity antagonist at functional α1-adrenoceptors with a selectivity α(1D) ≤ α(1A) > α(1B). In some tissues the compound exhibits an additional unsurmountable antagonist action, the clinical significance of which is unknown.

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DO - 10.1038/sj.bjp.0700907

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