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  • Title: Beta2-adrenergic receptor genotype-related changes in cAMP levels in peripheral blood mononuclear cells after multiple-dose oral procaterol.
    Author: Makimoto H, Sakaeda T, Nishiguchi K, Kita T, Sakai T, Komada F, Okumura K.
    Journal: Pharm Res; 2001 Dec; 18(12):1651-4. PubMed ID: 11785682.
    Abstract:
    PURPOSE: To evaluate the beta2-adrenergic receptor (beta2AR) genotype frequency in the Japanese population and the relationship between beta2AR genotype at amino acid position 16 (beta2AR-16) and desensitization to beta2-agonist ex vivo. METHODS: The beta2AR 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 beta2AR-16 genotype and the desensitization to beta2-agonist was examined in 10 male subjects ex vivo. Procaterol tablet (HCl salt, 50 microg, Meptin) 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 beta2-agonist was associated more frequently with the mutation at beta2AR-16 (Gly16).
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