Pharmacological characterization of α1- and β-adrenergic synergism of 5′DII activity in rat brown adipocytes

Abstract

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 β3- and α1-adrenergic agonists, BRL 37344 or CGP 12177, and cirazoline, in brown adipocytes. Inhibition of the α1- and β-adrenergic phenylephrine-stimulated 5′DII activity was obtained by the α1-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 α1-adrenergic antagonists in the order of prazosin > WB 4101 = benoxathian > 5-methylurapidil. Although the order of the α1-adrenergic competition seemed to be rather typical for the α1B-adrenergic receptors, a molecular analysis on adrenoceptor mRNAs should be made to confirm the exact α1-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 α1- and β-adrenoceptor subtypes participate in the regulation of 5′DII activity in the rat brown adipocytes, and therefore, an impaired α1- and β-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 α1-adrenoceptors in the BAT of obese Zucker rats is due to the decrease in the α1B-adrenoceptor subtype which would further be involved especially in the regulation of BAT 5′DII activity.