Langin D, Portillo M P, Saulnier-Blache J S, Lafontan M
INSERM Unité 317, Institut de Physiologie, Université Paul Sabatier, Toulouse, France.
Eur J Pharmacol. 1991 Jul 9;199(3):291-301. doi: 10.1016/0014-2999(91)90492-9.
The nature of the beta-adrenoceptors (beta-ARs) of the white fat cells of five mammalian species (rat, hamster, rabbit, dog and humans) was reassessed. The coexistence of at least three beta-ARs on the fat cell (except human) was demonstrated. Comparative binding and lipolysis studies were performed, using recently synthesized compounds selective for the atypical beta-AR of the rat brown fat cell and of the rat colon. beta 1- and beta 2-ARs have previously been identified in all the mammalian white fat cells using [125I]cyanopindolol ([125]CYP) or [3H]dihydroalprenolol. In addition to these receptors, we now demonstrated the existence of a third beta-AR directly involved in adrenergic-mediated lipolysis, and identified it in the white fat cells of the most commonly studied animal species, except humans. This receptor is not detected by the classically used beta-antagonist radioligands, explaining the discrepancies in reports on the nature of the beta-ARs of the adipose tissue. Pharmacological delineation of the third type of beta-AR-induced lipolysis showed this receptor to be rather similar to the previously proposed atypical beta-AR of brown and white rat fat cells. Its pharmacological properties were clarified, using new selective full agonists and partial agonists also acting as non-selective beta 1/beta 2-antagonists. The limits of [125]CYP as a radioligand were reported and the usefulness of BRL 37344, (+/-)-CGP 12177 and phenylethanolaminotralines derivatives (having an atypical beta-activity on intestinal motility) as major tools usable for atypical beta-AR activation was demonstrated. Moreover, confirming our previous results about the nature of the beta-ARs (beta 1- and beta 2-ARs) located in the fat cells of women (Mauriège et al., J. Lipid Res., 1987, 17, 156), no atypical beta-AR-mediated lipolysis was identified in abdominal adipose tissue from healthy women. The possible differences and similarities between this receptor and the recently cloned beta 3-AR are discussed.
对五种哺乳动物（大鼠、仓鼠、兔子、狗和人类）白色脂肪细胞的β-肾上腺素能受体（β-ARs）的性质进行了重新评估。结果表明，脂肪细胞（人类除外）上至少存在三种β-ARs。使用最近合成的对大鼠棕色脂肪细胞和大鼠结肠非典型β-AR具有选择性的化合物进行了比较结合和脂解研究。此前，已使用[125I]氰胍心安（[125]CYP）或[3H]二氢阿普洛尔在所有哺乳动物白色脂肪细胞中鉴定出β1-和β2-ARs。除了这些受体外，我们现在证明存在第三种直接参与肾上腺素能介导脂解的β-AR，并在除人类外最常研究的动物物种的白色脂肪细胞中鉴定出了它。经典使用的β-拮抗剂放射性配体未检测到这种受体，这解释了关于脂肪组织β-ARs性质的报道中的差异。对第三种类型的β-AR诱导的脂解进行药理学描述表明，这种受体与先前提出的大鼠棕色和白色脂肪细胞的非典型β-AR相当相似。使用新的选择性完全激动剂和部分激动剂（它们也作为非选择性β1/β2-拮抗剂起作用）阐明了其药理学特性。报告了[125]CYP作为放射性配体的局限性，并证明了BRL 37344、（±）-CGP 12177和苯乙醇胺三嗪衍生物（对肠道运动具有非典型β-活性）作为可用于非典型β-AR激活的主要工具的实用性。此外，证实了我们先前关于女性脂肪细胞中β-ARs（β1-和β2-ARs）性质的结果（Mauriège等人，《脂质研究杂志》，1987年，17卷，156页），在健康女性的腹部脂肪组织中未发现非典型β-AR介导的脂解。讨论了该受体与最近克隆的β3-AR之间可能的差异和相似之处。
