Premium
Ser 203 as well as Ser 204 and Ser 207 in fifth transmembrane domain of the human β 2 ‐adrenoceptor contributes to agonist binding and receptor activation
Author(s) -
Sato Takayuki,
Kobayashi Hiroyuki,
Nagao Taku,
Kurose Hitoshi
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702813
Subject(s) - isoprenaline , chemistry , agonist , alanine , ligand (biochemistry) , stereochemistry , receptor , serine , transmembrane domain , biochemistry , endocrinology , amino acid , biology , enzyme , stimulation
We examined the contribution of Ser 203 of the human β 2 ‐adrenoceptor (β 2 ‐AR) to the interaction with isoprenaline. The affinity of (−)‐isoprenaline was reduced by substitution of an alanine for Ser 203 , as well as for Ser 204 and Ser 207 . An (−)‐isoprenaline derivative with only one hydroxyl group, at the meta ‐position, showed reduced affinity for wild‐type β 2 ‐AR and S207A‐β 2 ‐AR and even lower affinities for S203A‐β 2 ‐AR and S204A‐β 2 ‐AR. By contrast, an (−)‐isoprenaline derivative with only a para ‐hydroxyl group showed reduced affinity for wild‐type β 2 ‐AR but the serine to alanine mutations did not cause further decreases. The EC 50 value for cyclic AMP generation in response to (−)‐isoprenaline was increased, by about 120 fold, for each alanine‐substituted β 2 ‐AR mutant. These results suggest that Ser 203 of the human β 2 ‐AR is important for both ligand binding and receptor activation. British Journal of Pharmacology (1999) 128 , 272–274; doi: 10.1038/sj.bjp.0702813