Differential regulation of β3-adrenoceptors in gut and adipose tissue of genetically obese (ob/ob) C57BL/6J-mice

Bronwyn A. Evans, Maria Papaioannou, Frank Anastasopoulos, Roger J. Summers

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Abstract

1. Levels of β3-adrenoceptor (AR) mRNA were compared using reverse transcription-polymerase chain reaction (RT-PCR) in white adipose tissue (WAT), brown adipose tissue (BAT), ileum and colon from genetically obese (ob/ob) and lean (+/+) C57BL/6J mice. Functional responses to the β3-AR agonist CL 316243 were also characterized in ileal longitudinal smooth muscle from obese and lean mice. 2. β3-AR mRNA levels were significantly higher in WAT (100 ± 16%) and BAT (100 ± 13%) from lean compared to WAT (21.0 ± 0.9%; n = 4; P < 0.005) and BAT (14.1 ± 2.2%; n = 5; P < 0.01) from obese mice. In contrast, β3-mRNA levels were not significantly different in ileum (100 ± 15%) and colon (100 ± 22%) from lean mice, compared to ileum (78 ± 13%; n = 4; P = 0.31) or colon (82 ± 15%; n = 4; P = 0.52) from obese mice. 3. Concentration-response curves to CL 316243 did not differ significantly in slope or position in ileal longitudinal smooth muscle from obese or lean mice. pEC50 (± s.e.mean) values were not significantly different (P = 0.59) between obese (7.90 ± 0.13, n = 7) and lean (7.77 ± 0.20, n = 7) mice. 4. pK(B) values for the β1-AR and β2-AR selective antagonist propranolol or the β3-AR selective antagonist SR 58894 against relaxations to CL 316243 were similar in ileum of genetically obese (propranolol 6.31 ± 0.22 and 6.13 ± 0.12; SR 58894 8.22 ± 0.06) and lean mice (propranolol 6.40 ± 0.08 and 6.60 ± 0.13; SR 58894 8.27 ± 0.12) and were consistent with values previously found at β3-AR. 5. Treatment of lean C57BL/6J mice with dexamethasone (1 mg kg-1, i.p.) significantly reduced β3-AR mRNA levels after 4 h in WAT (100 ± 6.1 to 41.4 ± 4.3; n = 16-18; P < 0.0001) and BAT (100 ± 8.0 to 35.1 ± 5.8; n = 17; P < 0.0001), but caused no change in ileum (100 ± 6.1 to 101 ± 17; n = 10-11; P = 0.95) or colon (100 ± 11 to 101 ± 11; n = 11; P = 0.94). β3-mRNA levels in ileum and colon also did not change significantly when examined over 24 h or after the administration of a higher dose of dexamethasone (5 mg kg-1). 6. In summary, β3-AR mRNA levels were considerably lower in WAT and BAT of obese compared to lean mice whereas the levels in ileum and colon were not significantly different. The similar β3-mRNA levels in ileum of obese and lean mice were associated with indistinguishable responses of carbachol-contracted ileum to a β3-agonist and similar affinity for β-antagonists. Administration of glucocorticoids to lean mice reduced β3-AR mRNA levels in WAT and BAT but not in ileum or colon. These studies show that in mice, β3-ARs are differentially regulated in ileum and colon compared to adipose tissues.

Original languageEnglish
Pages (from-to)763-771
Number of pages9
JournalBritish Journal of Pharmacology
Volume124
Issue number4
DOIs
Publication statusPublished - 26 Jun 1998

Keywords

  • β-adrenoceptors
  • Adipose tissue
  • CL 316243
  • Glucocorticoids
  • Gut
  • Obesity
  • Regulation
  • SR 58894

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