Effects of triiodothyronine administration on the adenylyl cyclase system in brown adipose tissue of rat.
This study was undertaken to investigate the effect of triiodothyronine (T3) administration to euthyroid rats on beta 3-adrenoceptor (beta 3-AR) expression and on the different components of the adenylyl cyclase (AC) system in brown adipose tissue (BAT). In rats treated with T3, the beta 3-AR density (assessed by the binding of [3H]CGP-12177) showed a decrease of 50%, as did their mRNA, as analyzed by reverse transcriptase-polymerase chain reaction. In hyperthyroid rats, compared with control rats, there was a 40% increase in G alpha s activity (stimulated by NaF or GTP gamma S) and a fourfold increase in the protein concentration (Western blotting). In contrast, the level of the pertussis toxin substrate Gi declined by 35% in response to T3. Analysis of dose-response curves for isoproterenol and CGP-12177 revealed that neither basal nor stimulated AC activities nor 50% stimulatory concentration for these agonists was changed by T3 administration. In conclusion, these results suggest that downregulation of the beta 3-AR by T3 was counter-balanced by changes in other components of the AC cascade (i.e., Gs and Gi), so no change occurred in the capacity of BAT to generate adenosine 3',5'-cyclic monophosphate.
Adli
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Laboratoire de Pharmacologie Clinique et Expérixentale, Faculté de Médecine, Université Paris Nord, Bobigny, France.
Bazin
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Vassy
R
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Perret
G Y
GY
D000262:Adenylyl Cyclases / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000201:enzymology*; D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000378:metabolism; D006980:Hyperthyroidism / Q000378:metabolism; D008297:Male; D011412:Propanolamines / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012016:Reference Values; D014284:Triiodothyronine / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; C033394:CGP 12177