Ser203 as well as Ser204 and Ser207 in fifth transmembrane domain of the human β2-adrenoceptor contributes to agonist binding and receptor activation

Takayuki Sato, Hiroyuki Kobayashi, Taku Nagao, Hitoshi Kurose

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

We examined the contribution of Ser203 of the human β2-adrenoceptor (β2-AR) to the interaction with isoprenaline. The affinity of (-)-isoprenaline was reduced by substitution of an alanine for Ser203, as well as for Ser204 and Ser207. An (-)-isoprenaline derivative with only one hydroxyl group, at the meta-position, showed reduced affinity for wild-type β2-AR and S207A-β2-AR and even lower affinities for S203A-β2-AR and S204A-β2-AR. By contrast, an (-)-isoprenaline derivative with only a para-hydroxyl group showed reduced affinity for wild-type β2-AR but the serine to alanine mutations did not cause further decreases. The EC50 value for cyclic AMP generation in response to (-)-isoprenaline was increased, by about 120 fold, for each alanine-substituted β2-AR mutant. These results suggest that Ser203 of the human β2-AR is important for both ligand binding and receptor activation.

Original languageEnglish
Pages (from-to)272-274
Number of pages3
JournalBritish Journal of Pharmacology
Volume128
Issue number2
DOIs
Publication statusPublished - 1999

All Science Journal Classification (ASJC) codes

  • Pharmacology

Fingerprint Dive into the research topics of 'Ser<sup>203</sup> as well as Ser<sup>204</sup> and Ser<sup>207</sup> in fifth transmembrane domain of the human β<sub>2</sub>-adrenoceptor contributes to agonist binding and receptor activation'. Together they form a unique fingerprint.

  • Cite this