Kurose H, Isogaya M, Kikkawa H, Nagao T
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
Life Sci. 1998;62(17-18):1513-7. doi: 10.1016/s0024-3205(98)00099-x.
We studied the binding region of several beta1 and beta2 selective agonists by using chimeric beta1 and beta2ARs, and point-mutated beta2 adrenergic receptors (ARs). By replacing a single transmembrane domain (TMD) of beta1AR (or beta2AR) with the corresponding region of beta2AR (or beta1AR), we found that beta2 or beta1 selectivities were determined by TMD2 and TMD7 of beta2AR or by TMD2 of beta1AR, respectively. Alanine-substituted beta2AR mutants showed that tyrosine at position 308 in TMD7 played an important role in binding of beta2 selective agonists with high affinity. These data also suggested that the substituent on the amine portion was important for subtype selective agonist binding.
我们通过使用嵌合β1和β2肾上腺素能受体（ARs）以及点突变的β2肾上腺素能受体，研究了几种β1和β2选择性激动剂的结合区域。通过用β2AR（或β1AR）的相应区域替换β1AR（或β2AR）的单个跨膜结构域（TMD），我们发现β2或β1选择性分别由β2AR的TMD2和TMD7或β1AR的TMD2决定。丙氨酸取代的β2AR突变体表明，TMD7中308位的酪氨酸在β2选择性激动剂的高亲和力结合中起重要作用。这些数据还表明，胺部分的取代基对于亚型选择性激动剂结合很重要。
