The in vivo effects of beta-3-receptor agonist CGP-12177 on thyroxine deiodination in cold-exposed, sympathectomized rat brown fat

Objective: The effects of the beta-3-receptor agonist CGP-12177 on thyroxine (T4) deiodination in sympathectomized (SX) interscapular brown adipose tissue (BAT) were assessed in 300 g body weight (BW) Wistar rats. Design: Seven days after SX, groups of rats were implanted s.c. with pellets containing 5 mg CGP12177 or 5 mg norepinephrine (NE) and were immediately placed at 4 8C for 24 h. Other SX groups were injected with CGP-12177 or NE 1 mg/kg BW i.p. and placed in the cold for 4 h. The latter group was injected, in addition, with prazosin 0.4 mg/100 g BW i.p. or propranolol 0.5 mg/100 g BW i.p. 15 min before and 2 h after the administration of CGP-12177 or NE. Methods: Two hours after the last injection of prazosin or propranolol, animals were killed and BAT was removed, homogenized and centrifuged at 500 g for 10 min at 4 8C. The infranatants were incubated during 60 min in the presence of dithiothreitol and 1 mCi [ 125 I]T4. Aliquots were chromatographed on paper for the measurement of [ 125 I]T4 and its deiodinated subproducts. Results: CGP-12177 restored normal T4 deiodination in SX BAT from both groups, but NE was slightly more effective. Propranolol, although not prazosin, blocked the CGP-12177 effects. Contrariwise, the NE-induced rise in deiodination was blocked by prazosin and to a lesser extent by propranolol. Conclusions: The results indicate that CGP-12177 stimulated the in vivo activation of 5 0 -deiodinase type II activity predominantly via beta-3-receptor, without participation of alpha-1-receptors.