Piétri-Rouxel F, Lenzen G, Kapoor A, Drumare M F, Archimbault P, Strosberg A D, Manning B S
Institut Cochin de Génétique Moléculaire, Centre Nationale de la Recherche Scientifique, UPR, Paris, France.
Eur J Biochem. 1995 May 15;230(1):350-8.
A full-length clone encoding a beta-adrenergic receptor was isolated from a bovine brown adipose tissue cDNA library. By comparative sequence analysis, and pharmacological characterization of a Chinese hamster ovary cell line expressing the full-length cDNA, it was shown that the product of the cloned gene is the bovine equivalent of the atypical beta 3-adrenergic receptor previously described in human, mouse, and rat [Strosberg, A. D. (1993) Prot. Sci. 2, 1198-1209]. The cloned receptor exhibits a pharmacological profile very similar to those from other species. In particular, the receptor has high affinity for BRL 37344 [(RR,SS)-(+/-)-4-(2'-[2-hydroxy-2-(3- chlorophenyl)ethylamino]propyl)phenoxyacetate sodium salt sesquihydrate], and low affinity for the iodinated ligand(-)-[3-125I]-iodocyanopindolol. The bovine beta 3-adrenergic receptor has high affinity for beta 1-adrenergic receptor and beta 2-adrenergic receptor antagonists including ICI 201651 [(R)-4-(2-hydroxy-3-phenoxypropylaminoethoxy)-N-(2- methoxyethyl)phenoxy acetic acid], carazolol, and CGP 12177A [(+/-)-4-(3-t-butylamino-2- hydroxypropoxy)benzimidazol-2-one]. In contrast to the murine beta 3-adrenergic receptor, both bupranolol and (-)-propranolol were partial agonists of the bovine receptor. The isolation of the bovine beta 3-adrenergic receptor, and information obtained from detailed pharmacological profiling may allow for the development of selective compounds for producing beef cattle with a low-body-mass index, and also aid the ongoing search for more selective agonists for the human receptor.
从牛棕色脂肪组织cDNA文库中分离出一个编码β-肾上腺素能受体的全长克隆。通过比较序列分析以及对表达全长cDNA的中国仓鼠卵巢细胞系进行药理学特性鉴定，结果表明克隆基因的产物是先前在人、小鼠和大鼠中描述的非典型β3-肾上腺素能受体的牛等同物[斯特罗斯伯格，A.D.（1993年）《蛋白质科学》2，1198 - 1209]。克隆的受体展现出与其他物种的受体非常相似的药理学特征。特别是，该受体对BRL 37344[（RR，SS）-（±）-4 - （2'-[2 - 羟基 - 2 - （3 - 氯苯基）乙氨基]丙基）苯氧基乙酸钠盐倍半水合物]具有高亲和力，而对碘化配体（-）-[3 - 125I] - 碘氰吲哚洛尔具有低亲和力。牛β3-肾上腺素能受体对包括ICI 201651[（R）-4 - （2 - 羟基 - 3 - 苯氧基丙基氨基乙氧基）-N - （2 - 甲氧基乙基）苯氧基乙酸]、卡唑洛尔和CGP 12177A[（±）-4 - （3 - 叔丁氨基 - 2 - 羟基丙氧基）苯并咪唑 - 2 - 酮]在内的β1-肾上腺素能受体和β2-肾上腺素能受体拮抗剂具有高亲和力。与小鼠β3-肾上腺素能受体不同，布普萘洛尔和（-）-普萘洛尔都是牛受体的部分激动剂。牛β3-肾上腺素能受体的分离以及从详细药理学分析中获得的信息可能有助于开发用于培育低体重指数肉牛的选择性化合物，并且也有助于正在进行的对人受体更具选择性激动剂的寻找。
