Muzzin P, Seydoux J, Giacobino J P, Venter J C, Fraser C
Département de Biochimie Médicale, Centre Médical Universitaire, Genève, Switzerland.
Biochem Biophys Res Commun. 1988 Oct 14;156(1):375-82. doi: 10.1016/s0006-291x(88)80851-9.
The novel brown adipose tissue (BAT) selective beta-adrenergic agonist, BRL 37344, is 31-fold more potent than (-)-isoproterenol in stimulating the respiratory rate of interscapular BAT fragments. BRL 37344 is also more potent (9-fold) than (-)-isoproterenol in stimulating adenylate cyclase activity of IBAT purified plasma membranes whereas, in the same preparation, it is 81-fold less potent than (-)-isoproterenol in competition displacement studies with the beta-adrenergic ligand, [125I]cyanopindolol. We have previously demonstrated that the photoaffinity reagent [125I]cyanopindolol-diazirine selectively labels a 62 kDa protein in IBAT plasma membranes that displays pharmacological properties of a beta 1-adrenergic subtype. Relatively high concentrations of BRL 37344 (10 microM) are required to displace [125I]cyanopindolol-diazirine binding to the 62 kDa protein. Taken together, the results suggest that two different populations of beta-adrenergic receptors may co-exist in BAT plasma membranes: a small population (about 15%) of atypical beta-receptors and a large population of beta 1-receptors that exhibit high and low affinities for BRL 37344, respectively.
新型棕色脂肪组织（BAT）选择性β-肾上腺素能激动剂BRL 37344在刺激肩胛间BAT碎片的呼吸速率方面比（-）-异丙肾上腺素强31倍。在刺激IBAT纯化质膜的腺苷酸环化酶活性方面，BRL 37344也比（-）-异丙肾上腺素更强（9倍），而在相同制剂中，在与β-肾上腺素能配体[125I]氰胍心安的竞争置换研究中，它比（-）-异丙肾上腺素弱81倍。我们之前已经证明，光亲和试剂[125I]氰胍心安-重氮苯选择性地标记IBAT质膜中一种62 kDa的蛋白质，该蛋白质表现出β1-肾上腺素能亚型的药理学特性。需要相对高浓度的BRL 37344（10 microM）才能取代[125I]氰胍心安-重氮苯与62 kDa蛋白质的结合。综上所述，结果表明两种不同类型的β-肾上腺素能受体可能共存于BAT质膜中：一小部分（约15%）非典型β-受体和一大部分β1-受体，它们分别对BRL 37344表现出高亲和力和低亲和力。
