Beta2-adrenergic receptor genotype-related changes in cAMP levels in peripheral blood mononuclear cells after multiple-dose oral procaterol.
OBJECTIVE
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).
Makimoto
H
H
Department of Hospital Pharmacy, School of Medicine, Kobe University, Japan.
Sakaeda
T
T
Nishiguchi
K
K
Kita
T
T
Sakai
T
T
Komada
F
F
Okumura
K
K
D000284:Administration, Oral; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000328:Adult; D000242:Cyclic AMP / Q000097:blood*; D015536:Down-Regulation; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D017265:Procaterol / Q000008:administration & dosage*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP; D017265:Procaterol