DIFFERENTIAL REGULATION OF BETA(3)-ADRENOCEPTORS IN GUT AND ADIPOSE-TISSUE OF GENETICALLY-OBESE (OB OB) C57BL/6J-MICE/

1 Levels of beta(3)-adrenoceptor (AR) mRNA were compared using reverse transcription-polymerase chain reaction (RT-PCR) in white adipose tis sue (WAT), brown adipose tissue (BAT), ileum and colon from geneticall y obese (ob/ob) and lean (+/+) C57BL/6J mice. Functional responses to the beta(3)-AR agonist CL 316243 were also characterized in ileal long itudinal smooth muscle from obese and lean mice. 2 beta(3)-AR mRNA lev els 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, beta(3 )-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 mi ce. 3 Concentration-response curves to CL 316243 did not differ signif icantly in slope or position in ileal longitudinal smooth muscle from obese or lean mice. pEC(50) (+/- s.e.mean) values were not significant ly 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 beta(1)-AR and bet a(2)-AR selective antagonist propranolol or the beta(3)-AR selective a ntagonist SR 58894 against relaxations to CL 316243 were similar in il eum 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 beta(3)-AR. 5 Treatment of lean C57BL/6J mice wit h dexamethasone (1 mg kg(-1), i.p.) significantly reduced beta(3)-AR m RNA 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). beta(3 )-mRNA levels in ileum and colon also did not change significantly whe n examined over 24 h or after the administration of a higher dose of d examethasone (5 mg kg(-1)). 6 In summary, beta(3)-AR mRNA levels were considerably lower in WAT and BAT of obese compared to lean mice where as the levels in ileum and colon were not significantly different. The similar beta(3)-mRNA levels in ileum of obese and lean mice were asso ciated with indistinguishable responses of carbachol-contracted ileum to a beta(3)-agonist and similar affinity for beta-antagonists. Admini stration of glucocorticoids to lean mice reduced beta(3)-AR mRNA level s in WAT and BAT but not in ileum or colon. These studies show that in mice, beta(3)-ARs are differentially regulated in ileum and colon com pared to adipose tissues.