Pharmacological characterization of alpha1- and beta-adrenergic synergism of 5'DII activity in rat brown adipocytes.
The role of adrenoceptor subtypes was studied in rat brown adipose tissue (BAT). The type II 5'-deiodinase (5'DII) was activated in response to simultaneous stimulation by beta3- and alpha1-adrenergic agonists, BRL 37344 or CGP 12177, and cirazoline, in brown adipocytes. Inhibition of the alpha1- and beta-adrenergic phenylephrine-stimulated 5'DII activity was obtained by the alpha1-adrenergic antagonists in the order of prazosin >/= wb 4101 > 5-methylurapidil. In comparison, the binding of [3H]prazosin to rat BAT plasma membranes was inhibited by alpha1-adrenergic antagonists in the order of prazosin > WB 4101 = benoxathian > 5-methylurapidil. Although the order of the alpha1-adrenergic competition seemed to be rather typical for the alpha1B-adrenergic receptors, a molecular analysis on adrenoceptor mRNAs should be made to confirm the exact alpha1-adrenergic subtypes at the level of brown adipocytes, since the possibility of a mixture of different receptor subtypes in brown fat cells and/or tissue may interact with the pharmacological characterization. Thus, specific alpha1- and beta-adrenoceptor subtypes participate in the regulation of 5'DII activity in the rat brown adipocytes, and therefore, an impaired alpha1- and beta-adrenergic co-work may be involved in a defective BAT function, e.g., in obese Zucker rats, too. An interesting possibility is that the decreased number of alpha1-adrenoceptors in the BAT of obese Zucker rats is due to the decrease in the alpha1B-adrenoceptor subtype which would further be involved especially in the regulation of BAT 5'DII activity.
Raasmaja
Atso
A
Department of Pharmacology & Toxicology, University of Helsinki, Helsinki, Finland. atso.raasmaja@helsinki.fi
York
David A
DA
D002001:Adipose Tissue, Brown / Q000201:enzymology / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004357:Drug Synergism; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010075:Oxathiins / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014284:Triiodothyronine / Q000097:blood
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D007093:Imidazoles; D010075:Oxathiins; D010879:Piperazines; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; C057446:5-methylurapidil; C057368:BRL 37344; C050877:benoxathian; D007453:Iodide Peroxidase; C014282:cirazoline; C033394:CGP 12177; D011224:Prazosin