β1-adrenoceptors compensate for β3-adrenoceptors in ileum from β3-adrenoceptor knock-out mice

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Abstract

1. This study examines β1-, β2- and β3-adrenoceptor (AR)-mediated responses, mRNA levels and radioligand binding in ileum from β3-AR knock-out (-/-) (KO) and wild type (+/+) (FVB) mice. 2. In KO and FVB mice, SR59230A (100 nM) (β3-AR antagonist) antagonized responses to (-)-isoprenaline in both KO and FVB mice. (-)-Isoprenaline mediated relaxation of ileum was antagonized weakly by ICI118551 (100 nM) (β2-AR antagonist). Responses to (-)-isoprenaline were more strongly antagonized by CGP20712A (100 nM) (β1-AR antagonist), propranolol (1 μM) (β1-/β2-AR antagonist), carvedilol (100 nM) (non-specific β-AR antagonist), and CGP12177A (100 nM) (β1-/β2-AR antagonist) in ileum from KO than in FVB mice. 3. Responses to CL316243 (β3-AR agonist) in ileum from FVB mice were antagonized by SR59230A (100 nM) but not by propranolol (1 μM) or carvedilol (100 nM). CL316243 was ineffective in relaxing ileum from KO mice. 4. CGP12177A had no agonist actions in ileum from either KO or FVB mice. 5. β1-AR mRNA levels were increased 3 fold in ileum from KO compared to FVB mice. This was associated with an increased maximum number of β1-/β2-AR binding sites (Bmax). β2-AR mRNA levels were unaffected while no β3-AR mRNA was detected in KO mice. 6. In mouse ileum, β3-ARs and to a lesser extent β1-ARs are the predominant adrenoceptor subtypes mediating relaxation in ileum from FVB mice. In KO mice β1-ARs functionally compensate for the lack of β3-ARs, and this is associated with increased β1-AR mRNA and levels of binding.

Original languageEnglish
Pages (from-to)433-442
Number of pages10
JournalBritish Journal of Pharmacology
Volume132
Issue number2
DOIs
Publication statusPublished - 1 Jan 2001

Keywords

  • (-)-isoprenaline
  • CG P12177A
  • CL316243
  • Ileum
  • Knock-out

Cite this

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title = "β1-adrenoceptors compensate for β3-adrenoceptors in ileum from β3-adrenoceptor knock-out mice",
abstract = "1. This study examines β1-, β2- and β3-adrenoceptor (AR)-mediated responses, mRNA levels and radioligand binding in ileum from β3-AR knock-out (-/-) (KO) and wild type (+/+) (FVB) mice. 2. In KO and FVB mice, SR59230A (100 nM) (β3-AR antagonist) antagonized responses to (-)-isoprenaline in both KO and FVB mice. (-)-Isoprenaline mediated relaxation of ileum was antagonized weakly by ICI118551 (100 nM) (β2-AR antagonist). Responses to (-)-isoprenaline were more strongly antagonized by CGP20712A (100 nM) (β1-AR antagonist), propranolol (1 μM) (β1-/β2-AR antagonist), carvedilol (100 nM) (non-specific β-AR antagonist), and CGP12177A (100 nM) (β1-/β2-AR antagonist) in ileum from KO than in FVB mice. 3. Responses to CL316243 (β3-AR agonist) in ileum from FVB mice were antagonized by SR59230A (100 nM) but not by propranolol (1 μM) or carvedilol (100 nM). CL316243 was ineffective in relaxing ileum from KO mice. 4. CGP12177A had no agonist actions in ileum from either KO or FVB mice. 5. β1-AR mRNA levels were increased 3 fold in ileum from KO compared to FVB mice. This was associated with an increased maximum number of β1-/β2-AR binding sites (Bmax). β2-AR mRNA levels were unaffected while no β3-AR mRNA was detected in KO mice. 6. In mouse ileum, β3-ARs and to a lesser extent β1-ARs are the predominant adrenoceptor subtypes mediating relaxation in ileum from FVB mice. In KO mice β1-ARs functionally compensate for the lack of β3-ARs, and this is associated with increased β1-AR mRNA and levels of binding.",
keywords = "(-)-isoprenaline, CG P12177A, CL316243, Ileum, Knock-out",
author = "Hutchinson, {D. S.} and Evans, {B. A.} and Summers, {R. J.}",
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β1-adrenoceptors compensate for β3-adrenoceptors in ileum from β3-adrenoceptor knock-out mice. / Hutchinson, D. S.; Evans, B. A.; Summers, R. J.

In: British Journal of Pharmacology, Vol. 132, No. 2, 01.01.2001, p. 433-442.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - β1-adrenoceptors compensate for β3-adrenoceptors in ileum from β3-adrenoceptor knock-out mice

AU - Hutchinson, D. S.

AU - Evans, B. A.

AU - Summers, R. J.

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N2 - 1. This study examines β1-, β2- and β3-adrenoceptor (AR)-mediated responses, mRNA levels and radioligand binding in ileum from β3-AR knock-out (-/-) (KO) and wild type (+/+) (FVB) mice. 2. In KO and FVB mice, SR59230A (100 nM) (β3-AR antagonist) antagonized responses to (-)-isoprenaline in both KO and FVB mice. (-)-Isoprenaline mediated relaxation of ileum was antagonized weakly by ICI118551 (100 nM) (β2-AR antagonist). Responses to (-)-isoprenaline were more strongly antagonized by CGP20712A (100 nM) (β1-AR antagonist), propranolol (1 μM) (β1-/β2-AR antagonist), carvedilol (100 nM) (non-specific β-AR antagonist), and CGP12177A (100 nM) (β1-/β2-AR antagonist) in ileum from KO than in FVB mice. 3. Responses to CL316243 (β3-AR agonist) in ileum from FVB mice were antagonized by SR59230A (100 nM) but not by propranolol (1 μM) or carvedilol (100 nM). CL316243 was ineffective in relaxing ileum from KO mice. 4. CGP12177A had no agonist actions in ileum from either KO or FVB mice. 5. β1-AR mRNA levels were increased 3 fold in ileum from KO compared to FVB mice. This was associated with an increased maximum number of β1-/β2-AR binding sites (Bmax). β2-AR mRNA levels were unaffected while no β3-AR mRNA was detected in KO mice. 6. In mouse ileum, β3-ARs and to a lesser extent β1-ARs are the predominant adrenoceptor subtypes mediating relaxation in ileum from FVB mice. In KO mice β1-ARs functionally compensate for the lack of β3-ARs, and this is associated with increased β1-AR mRNA and levels of binding.

AB - 1. This study examines β1-, β2- and β3-adrenoceptor (AR)-mediated responses, mRNA levels and radioligand binding in ileum from β3-AR knock-out (-/-) (KO) and wild type (+/+) (FVB) mice. 2. In KO and FVB mice, SR59230A (100 nM) (β3-AR antagonist) antagonized responses to (-)-isoprenaline in both KO and FVB mice. (-)-Isoprenaline mediated relaxation of ileum was antagonized weakly by ICI118551 (100 nM) (β2-AR antagonist). Responses to (-)-isoprenaline were more strongly antagonized by CGP20712A (100 nM) (β1-AR antagonist), propranolol (1 μM) (β1-/β2-AR antagonist), carvedilol (100 nM) (non-specific β-AR antagonist), and CGP12177A (100 nM) (β1-/β2-AR antagonist) in ileum from KO than in FVB mice. 3. Responses to CL316243 (β3-AR agonist) in ileum from FVB mice were antagonized by SR59230A (100 nM) but not by propranolol (1 μM) or carvedilol (100 nM). CL316243 was ineffective in relaxing ileum from KO mice. 4. CGP12177A had no agonist actions in ileum from either KO or FVB mice. 5. β1-AR mRNA levels were increased 3 fold in ileum from KO compared to FVB mice. This was associated with an increased maximum number of β1-/β2-AR binding sites (Bmax). β2-AR mRNA levels were unaffected while no β3-AR mRNA was detected in KO mice. 6. In mouse ileum, β3-ARs and to a lesser extent β1-ARs are the predominant adrenoceptor subtypes mediating relaxation in ileum from FVB mice. In KO mice β1-ARs functionally compensate for the lack of β3-ARs, and this is associated with increased β1-AR mRNA and levels of binding.

KW - (-)-isoprenaline

KW - CG P12177A

KW - CL316243

KW - Ileum

KW - Knock-out

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DO - 10.1038/sj.bjp.0703828

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JO - British Journal of Pharmacology

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