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

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