Garruti G, De Pergola G, Cignarelli M, Stock M, Giorgino R
Clinica Medica III, Università di Bari.
Minerva Endocrinol. 1990 Apr-Jun;15(2):125-9.
Some sympathomimetic compounds (i.e. BRL37344) increase brown adipose tissue (BAT) thermogenesis with minimal cardiac effects. They act through an "atypical" beta-adrenergic receptor (beta-AR). Since beta-AR responses involve Adenylate Cyclase (AC) activation, we investigate the AC answer to isoproterenol and BRL37344 in rat plasmamembranes of heart (beta 1-ARs) and BAT (atypical beta-ARs). AC dose-response curves were obtained by incubating membrane fractions with different concentrations of isoproterenol and BRL37344 (1 nM-100 microM) at 25 degrees C for 15 min. In our study BRL37344 is 40-times more potent than isoproterenol in stimulating AC activity of BAT (EC50s: BRL37344 = 0.02 microM, isoproterenol = 0.7 microM). Furthermore it is more potent in stimulating BAT AC than heart AC (BRL37344 EC50 ratio heart/BAT = 38). However on BAT membranes, BRL37344 intrinsic sympathomimetic activity (ISA) vs. Isoproterenol is 0.87. Since isoproterenol and BRL37344 show a similar ISA for BAT respiration and lipolysis, we may argue that AC maximal activity is not required for maximal lipolytic and thermogenic responses.
一些拟交感神经化合物（如BRL37344）可增加棕色脂肪组织（BAT）的产热，且对心脏的影响极小。它们通过一种“非典型”β-肾上腺素能受体（β-AR）发挥作用。由于β-AR反应涉及腺苷酸环化酶（AC）的激活，我们研究了大鼠心脏（β1-ARs）和BAT（非典型β-ARs）质膜中AC对异丙肾上腺素和BRL37344的反应。通过在25℃下将膜片段与不同浓度的异丙肾上腺素和BRL37344（1 nM - 100 μM）孵育15分钟，获得AC剂量反应曲线。在我们的研究中，BRL37344刺激BAT的AC活性的效力比异丙肾上腺素高40倍（半数有效浓度：BRL37344 = 0.02 μM，异丙肾上腺素 = 0.7 μM）。此外，它刺激BAT的AC比刺激心脏的AC更有效（BRL37344的心脏/ BAT半数有效浓度比值 = 38）。然而，在BAT膜上，BRL37344相对于异丙肾上腺素的内在拟交感活性（ISA）为0.87。由于异丙肾上腺素和BRL37344对BAT呼吸和脂解表现出相似的ISA，我们可以认为最大的脂解和产热反应不需要AC的最大活性。
