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.


METHODS
Seven days after SX, groups of rats were implanted s.c. with pellets containing 5mg CGP-12177 or 5mg norepinephrine (NE) and were immediately placed at 4 degrees C for 24h. Other SX groups were injected with CGP-12177 or NE 1mg/kg BW i. p. and placed in the cold for 4h. The latter group was injected, in addition, with prazosin 0.4 mg/100g BW i.p. or propranolol 0.5mg/100g BW i.p. 15 min before and 2h 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 degrees C. The infranatants were incubated during 60 min in the presence of dithiothreitol and 1 microCi [(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'-deiodinase type II activity predominantly via beta-3-receptor, without participation of alpha-1-receptors.
Department of Zoology, University of Graz, Austria.
D
D
Hofer
M
M
Raíces
K
K
Schauenstein
S
S
Porta
W
W
Korsatko
K
K
Hagmüller
A
A
Zaninovich
D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003080:Cold Temperature; D004343:Drug Implants; D004789:Enzyme Activation / Q000187:drug effects; D007453:Iodide Peroxidase / Q000378:metabolism*; D007455:Iodine / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013562:Sympathectomy; D013974:Thyroxine / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004343:Drug Implants; D007457:Iodine Radioisotopes; D011412:Propanolamines; D007455:Iodine; D011433:Propranolol; D007453:Iodide Peroxidase; D013974:Thyroxine; C033394:CGP 12177; D009638:Norepinephrine; D011224:Prazosin