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β2-Adrenergic Receptor Genotype-Related Changes in cAMP Levels in Peripheral Blood Mononuclear Cells After Multiple-Dose Oral Procaterol

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Abstract

Purpose. To evaluate the β2-adrenergic receptor (β2AR) genotype frequency in the Japanese population and the relationship between β2AR genotype at amino acid position 16 (β2AR-16) and desensitization to β2-agonist ex vivo.

Methods. The β2AR 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 β2AR-16 genotype and the desensitization to β2-agonist was examined in 10 male subjects ex vivo. Procaterol tablet (HCl salt, 50μg, 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 β2-agonist was associated more frequently with the mutation at β2AR-16 (Gly16).

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Author notes

  1. Fusao Komada

    Present address: Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Josai University, Saitama, 350-0290, Japan

Authors and Affiliations

  1. Department of Hospital Pharmacy, School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Hiroo Makimoto, Toshiyuki Sakaeda, Kohshi Nishiguchi, Tomoko Kita, Fusao Komada & Katsuhiko Okumura

  2. Second Department of Internal Medicine, School of Medicine, Kobe University, Kobe, 650-0017, Japan

    Toshiyuki Sakai

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Makimoto, H., Sakaeda, T., Nishiguchi, K. et al. β2-Adrenergic Receptor Genotype-Related Changes in cAMP Levels in Peripheral Blood Mononuclear Cells After Multiple-Dose Oral Procaterol. Pharm Res 18, 1651–1654 (2001). https://doi.org/10.1023/A:1013354025731

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