β3-adrenoceptor regulation and relaxation responses in mouse ileum

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Abstract

1. This study examines the relationship between β(3a)- and β(3b)-adrenoceptor (AR) mRNA levels, β3-AR binding and changes in ileum responses in mice treated with the β3-AR agonist (R,R)-5-[2[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]-propyl]1,3-benzodioxole-2,2-dicarboxylate (CL316243), or the β3-AR antagonist 3-(2-ethylphenoxy)-l-[(1S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanol oxalate (SR59230A), or dexamethasone or forskolin. 2. Levels of β(3a)- and β(3b)-AR mRNA and the maximum number of binding sites (B(max)) in ileum were unaffected following CL316243 treatment, although responses to CL316243 were reduced by 50% following 4 and 24 h treatment, indicating another desensitization mechanism not involving changes in receptor expression or number. β(3a)-AR mRNA levels were reduced in both brown (BAT) and white adipose tissue (WAT) but β(3b)-AR mRNA levels were significantly reduced only in WAT. Levels of β(3a)- and β(3b)-mRNA returned towards normal with continued treatment. 3. SR59230A treatment markedly increased β3-AR mRNA levels in ileum and BAT but not in WAT. The increase in β3-AR mRNA levels in ileum was associated with increased B(max) levels in binding analysis and increased responses to CL316243, suggesting these as the cause of sensitization. 4. Treatment with forskolin (4 h) or dexamethasone (4 h) significantly reduced β(3a)-AR mRNA levels in BAT and WAT but did not alter levels in ileum. Responses to CL316243 in ileum were unaffected by either treatment. 5. In summary, the β3-AR is differently regulated in adipose tissue and ileum: Treatment with SR59230A increased β3-AR number, mRNA and responsiveness in ileum, whereas treatment with CL316243 reduced responses without affecting β3-AR number or mRNA levels.

Original languageEnglish
Pages (from-to)1251-1259
Number of pages9
JournalBritish Journal of Pharmacology
Volume129
Issue number6
DOIs
Publication statusPublished - 1 Jan 2000

Keywords

  • Adipose tissue
  • CL316243
  • Ileum
  • Mouse
  • Regulation
  • SR59230A

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