Binding domains of the β-adrenergic receptors for β1 and β2- selective agonists

Hitoshi Kurose, Hideo Kikkawa, Masafumi Isogaya, Taku Nagao

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Structural basis of the β-adrenergic receptor (βAR) to confer the β selectivity is largely unknown. We investigated the binding regions of βAR which is important for the subtype selective binding. TA-2005 is a highly selective β2 agonist with the carbostyril structure. Binding regions of the βAR for TA-2005 was investigated by use of chimeric β1 and β2 receptors as compared with those of non-selective β agonist isoproterenol. Replacement of transmembrane region 2 (TM2) or TM7 of β2AR with those of β1AR decreased the affinity of TA-2005. Deletion of methoxyphenyl group from TA- 2005 molecule lost β2 selectivity. Then it is reasonable to assume that methoxyphenyl group interacts with TM2 and TM7 of β2AR, and contributes to the β2 selectivity. Several β2 selective agonists including formoterol and salmeterol also required TM2 or TM7 for the β2 selective binding. T- 0509 is a β1 selective full agonist. In contrast with the binding of β2 selective agonist, selective binding of T-0509 to β1AR required the only TM2 of β1AR. These data suggested that TM2 and TM7 of βAR is important for the subtype selective binding.

Original languageEnglish
Pages (from-to)75P-80P
JournalFolia Pharmacologica Japonica
Issue numberSUPPL. 1
Publication statusPublished - 1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology


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