Puigserver P, Picó C, Stock M J, Palou A
Dept. de Biologia Fonamental i Ciències de la Salut, Universitat de les Illes Balears, Palma de Mallorca, Spain.
Mol Cell Endocrinol. 1996 Mar 1;117(1):7-16. doi: 10.1016/0303-7207(95)03727-6.
Given the co-existence of the three beta-adrenoceptor (beta AR) subtypes (beta 1AR, beta 2AR and beta 3AR) in brown adipocytes, the present study was undertaken to determine the relative importance of these in the induction of UCP synthesis in mouse BAT precursor cells in primary culture. Cells at different stages of differentiation were exposed to different beta AR agonists: prenalterol (a selective beta 1AR agonist), salbutamol or clenbuterol (selective beta 2AR agonists), or BRL 37344 (a selective beta 3AR agonist). As with the endogenous agonist, noradrenaline, and the non-selective beta AR agonist, isoprenaline, all four beta AR agonists induced UCP in the confluent stage of the cells, but with different potencies, and with the highest induction being seen after clenbuterol or BRL 37344 treatment. Cells in the confluent stage of development were the most sensitive to the effects of the agonists, although clenbuterol and BRL 37344 induced a weak UCP synthesis in pre-confluent cells. None of these beta AR agonists were able to induce UCP synthesis in the post-confluent period. The responses to prenalterol and salbutamol were inhibited by propranolol at relatively low concentrations, suggesting their effects were mediated by beta 1AR and beta 2AR, respectively. However, propranolol was a particularly weak antagonist of BRL 37344 and, unexpectedly, of the clenbuterol UCP responses, which suggests that both induce UCP synthesis via the beta 3AR. In summary, the beta 3AR is the most important adrenoceptor coupled to the induction of UCP synthesis, although both beta 1AR and beta 2AR activation may make a contribution. However, all three beta AR subtypes do not become fully functional until cultured cells become confluent.
鉴于棕色脂肪细胞中存在三种β-肾上腺素能受体（β-AR）亚型（β1AR、β2AR和β3AR），本研究旨在确定它们在原代培养的小鼠棕色脂肪组织（BAT）前体细胞中诱导解偶联蛋白（UCP）合成的相对重要性。将处于不同分化阶段的细胞暴露于不同的β-AR激动剂：普瑞特罗（一种选择性β1AR激动剂）、沙丁胺醇或克伦特罗（选择性β2AR激动剂），或BRL 37344（一种选择性β3AR激动剂）。与内源性激动剂去甲肾上腺素和非选择性β-AR激动剂异丙肾上腺素一样，所有四种β-AR激动剂在细胞汇合阶段均能诱导UCP生成，但效力不同，克伦特罗或BRL 37344处理后诱导作用最强。处于发育汇合阶段的细胞对激动剂的作用最为敏感，尽管克伦特罗和BRL 37344在汇合前细胞中诱导较弱的UCP合成。这些β-AR激动剂在汇合后阶段均不能诱导UCP合成。普萘洛尔在相对较低浓度下可抑制对普瑞特罗和沙丁胺醇的反应，表明它们的作用分别由β1AR和β2AR介导。然而，普萘洛尔对BRL 37344以及出乎意料地对克伦特罗诱导的UCP反应是一种特别弱的拮抗剂，这表明两者均通过β3AR诱导UCP合成。总之，β3AR是与UCP合成诱导相关的最重要的肾上腺素能受体，尽管β1AR和β2AR的激活也可能起一定作用。然而，在培养细胞汇合之前，所有三种β-AR亚型都不会完全发挥功能。
