Identification and Characterization of the Imidazoline I2b-binding Sites in the Hamster Brown Adipose Tissue as a Study Model for Imidazoline Receptors

• Published in: Archives of physiology and biochemistry Vol. 111; no. 2; pp. 159 - 166
• Main Authors: Römer, L., Wurster, S., Savola, J.-M., Raasmaja, A.
• Format: Journal Article
• Language: English
• Published: Basingstoke Informa UK Ltd 01.04.2003; Taylor & Francis
• Subjects: Adipose Tissue, Brown - chemistry; Adipose Tissue, Brown - metabolism; Amiloride - chemistry; Amiloride - pharmacokinetics; Animals; Binding Sites; Binding, Competitive; Biological and medical sciences; Cell Line, Tumor; Clonidine - chemistry; Clonidine - pharmacokinetics; Culture Techniques; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Guanabenz - chemistry; Guanabenz - pharmacokinetics; Humans; Idazoxan - chemistry; Idazoxan - pharmacokinetics; Imidazoles - chemistry; Imidazoles - pharmacokinetics; Imidazoline Receptors; Liver - chemistry; Liver - metabolism; Mammary Neoplasms, Animal; Mice; Protein Binding; Rats; Receptors, Drug - chemistry; Receptors, Drug - metabolism; Species Specificity; Vertebrates: skin, associated glands, phaneres, light organs, various exocrine glands (salt gland, uropygial gland...), adipose tissue, connective tissue; Yohimbine - chemistry; Yohimbine - pharmacokinetics; brown adipose tissue (BAT); Rodentia; Brown adipose tissue; Binding site; I2 Imidazoline receptor; Modeling; Vertebrata; Mammalia; Animal; 3H-idazoxan; Imidazoline I2b-receptor; Models; Hamster; Biological receptor
• ISSN: 1381-3455; 1744-4160
• DOI: 10.1076/apab.111.2.159.14006

The imidazoline-type compound, MPV-1743, has been found to activate nonshivering thermogenesis (NST) in brown adipose tissue (BAT) of the genetically obese Zucker rats. The regulation of NST in BAT is linked to the catecholamine metabolism, and the imidazoline I 2 -binding sites have been found on the monoamine oxidase, a catecholamine metabolising enzyme. In this study, the I 2 -binding sites of hamster BAT have been characterised using a receptor binding assay with 3 H-idazoxan as a radioligand, and the interaction of MPV-1743 with these I 2 -binding sites has been studied using the enantiomers of MPV 1743, that is, MPV 2088 and MPV 2089. Cirazoline was used to determine the specific binding of 3 H-idazoxan to the imidazoline I 2 -binding sites. Rauwolscine was added in the 3 H-idazoxan binding assay in order to inhibit any binding to potential a 2 -adrenergic sites. In the presence of rauwolscine mask 3 H-Idazoxan labelled a population of non-adrenergic binding sites expressing the properties of the imidazoline I 2b -receptor subtype similar to that found in the rat liver (cirazoline » guanabenz = amiloride » clonidine). The binding of 3 H-idazoxan to the I 2b -binding sites could be displaced by the imidazole compounds with the following affinities: detomidine (K iHigh 9.2nM; K iLow 3200nM), MPV-2088 (K iHigh 19nM; K iLow 760nM) and MPV-2089 (K iHigh 190nM; K iLow 1300 nM), atipamezole (3500 nM) and dexmedetomidine (K i 8400 nM). These results have shown that the hamster BAT contains the imidazoline I 2b -binding sites with heterogeneous binding properties for some test compounds. In addition, the enantiomers of MPV 1743, that is, MPV 2088 and MPV 2089, had high affinity to these BAT imidazoline I 2b -binding sites. Therefore, it is suggested that the regulation of NST in the hamster BAT may be an attractive model to study the role of imidazoline I 2b -binding sites.