β2-adrenergic receptor genotype-related changes in cAMP levels in peripheral blood mononuclear cells after multiple-dose oral procaterol

Purpose. To evaluate the beta (2)-adronergic receptor (beta (2)AR) genotype frequency in the Japanese population and the relationship between,AR genotype at amino acid position 16 ( beta (2)AR-16) and desensitization to beta (2)-agonist ex vivo. Methods. The beta (2)AR genotypes at amino acid positions 16, 27, and 164 of 92 healthy Japanese subjects were determined by polymerase chain reaction-restriction fragment-length polymorphism. The relationship between the beta (2)AR-16 genotype and the desensitization to beta (2)-agonist was examined in 10 male subjects ex vivo. Procaterol tablet (HCl salt, 50 mug, Meptin(R)) was given orally for 5 days, and peripheral blood was obtained before and after 5 days of consecutive medications followed by the assessment of the intracellular cAMP levels in peripheral blood mononuclear cells after incubation with or without procaterol hydrochloride (0-1000 ng/mL). Results. Allele frequency was Arg16:Gly16 = 46%:54%, Gln27: Glu27 = 92%:8%, and Thr164:Ile164 = 100%:0%, respectively. The cAMP levels were increased by incubation with procaterol hydrochloride, and the increase was suppressed after 5 days of consecutive medications. The suppression was more significant in the homozygote for Gly16 than the homozygote for Arg16. Conclusions. The desensitization to beta (2)-agonist was associated more frequently with the mutation at beta (2)AR-16 (Gly16).