The imidazoline I₂-site ligands BU 224 and 2-BFI inhibit MAO-A and MAO-B activities, hydrogen peroxide production, and lipolysis in rodent and human adipocytes

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• 作者：Sandy Bour ; Marí ; a-Carmen Iglesias-Osma ; Luc Marti ; Piedad Duro ; Marí ; a-José ; Garcia-Barrado ; Maria-Francisca Pastor ; Danielle Pré ; vot ; Virgile Visentin ; Philippe Valet ; Julio Moratino
• 关键词：Imidazoline site ligand ; Insulin ; MAO (Monoamine oxidase) ; SSAO (Semicarbazide-sensitive amine oxidase) ; Adipose tissue
• 刊名：European Journal of Pharmacology
• 出版年：2006
• 出版时间：15 December 2006
• 年：2006
• 卷：552
• 期：1-3
• 页码：20-30
• 全文大小：424 K

文摘

Numerous imidazolinic agents exhibit antihyperglycaemic properties and have been described to promote insulin secretion, however their effects on adipose tissue development have been poorly investigated. Since white adipose tissue (WAT) plays an important role in glucose homeostasis and expresses imidazoline (I₂) binding sites abundantly, this work aimed at studying extrapancreatic actions of two I₂-site ligands, BU 224 and 2-BFI in adipocytes. Interaction with monoamine oxidase (MAO) was investigated by measuring the ability to modulate [¹⁴C]tyramine oxidation and hydrogen peroxide production. Direct influence on glucose uptake or on lipolytic activity was tested on mouse, rat, rabbit and human adipocytes. BU 224 and 2-BFI behaved as reversible inhibitors of both MAO-A and -B, as demonstrated by total inhibition of tyramine oxidation in human adipocytes and platelets or in liver from rats previously treated with selective MAO-inhibitors. Moreover, they weakly inhibited semicarbazide-sensitive amine oxidase. Like classical MAO-inhibitors, they were unable to produce hydrogen peroxide and to activate glucose uptake but prevented tyramine to do so in rodent or human adipocytes. BU 224 and 2-BFI also differed from MAO-inhibitors since they inhibited lipolysis at millimolar concentrations via a still undefined pathway independent of α₂-adrenoceptor stimulation, β-adrenergic antagonism and MAO activation. However, chronic treatment of obese Zucker rats with 2-BFI did not modify the maximal lipolytic capacity or the mild insulin resistance status of their adipocytes. Taken together, our observations demonstrate on WAT novel effects of BU 224 and 2-BFI different from their already reported actions on brain or endocrine pancreas.