COEXISTENCE OF 3 BETA-ADRENOCEPTOR SUBTYPES IN WHITE FAT-CELLS OF VARIOUS MAMMALIAN-SPECIES
COEXISTENCE OF 3 BETA-ADRENOCEPTOR SUBTYPES IN WHITE FAT-CELLS OF VARIOUS MAMMALIAN-SPECIES
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DOI：
10.1016/0014-2999(91)90492-9
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发表时间：
1991-07-09
影响因子：
5
通讯作者：
LAFONTAN, M
中科院分区：
文献类型：
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作者：
LANGIN, D;PORTILLO, MP;LAFONTAN, M
重新评估了5种哺乳动物（大鼠、仓鼠、兔、犬和人）白色脂肪细胞的β-肾上腺素受体（β-AR）的性质。证明脂肪细胞（人类除外）上至少有三种β-AR共存。使用最近合成的对大鼠棕色脂肪细胞和大鼠结肠的非典型β-AR具有选择性的化合物进行比较结合和脂解研究。先前已使用[I-125]氰基吲哚洛尔（[125] NH 4）或[H-3]二氢烯丙洛尔在所有哺乳动物白色脂肪细胞中鉴定出β-1-和β-2-AR。除了这些受体外，我们现在还证实了第三种β-AR的存在，它直接参与肾上腺素能介导的脂解作用，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它。该受体未被传统使用的β-拮抗剂放射性配体检测到，这解释了关于脂肪组织β-AR性质的报告中的差异。第三种β-AR诱导的脂解作用的药理学描述表明，这种受体与先前提出的棕色和白色大鼠脂肪细胞的非典型β-AR非常相似。使用新的选择性完全激动剂和部分激动剂也作为非选择性β-1/β-2-拮抗剂，阐明了其药理学特性。报告了[125] BRL作为放射性配体的限度，并证明了BRL 37344、（+/-）-CGP 12177和苯乙醇氨基萘衍生物（对肠蠕动具有非典型β活性）作为非典型β-AR激活的主要工具的有用性。此外，证实了我们先前关于位于女性脂肪细胞中的β-AR（β-1-和β-2-AR）的性质的结果（Mauriege等人，J. Lipid Res.，1987，17，156），在来自健康女性的腹部脂肪组织中未鉴定到非典型β-AR介导的脂解。这种受体和最近克隆的β-3-AR之间可能存在的差异和相似之处进行了讨论。
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 [I-125]cyanopindolol ([125]CYP) or [H-3]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 (Mauriege 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.