Yamasaki Yasuhiro, Kishimoto Nobuhito, Ohnishi Hisako, Fujita Jiro, Kobayashi Makoto, Kamei Tadashi, Tada Shinya, Ueda Nobuo
Takamatsu Municipal Hospital, 2-36-1, Miyawaki-cho, Takamatsu-city, 760-8538, Japan.
Nihon Kokyuki Gakkai Zasshi. 2004 Mar;42(3):239-46.
It has been suggested that the Arg 16/Gly 16 allele at codon 16 of beta 2-adrenoceptor polymorphism plays a role in down-regulating the stimulus of bronchodilatation caused by beta 2-agonists. This study was designed to evaluate the difference of bronchodilator responsiveness to beta 2-agonist (procaterol) and anti-cholinergic drug (oxitropium) between those who have Arg 16/Gly 16 allele (hetero type) and those who have Gly 16/Gly 16 allele (variant type) at codon 16 of in healthy women. Airway resistance and other pulmonary function tests were measured by a body plethysmography before and 5, 10, 15, 20, and 30 minutes after inhalation of procaterol or inhalation of procaterol and oxitropium. In healthy women inhaled procaterol, percent changes of respiratory airway resistance compared with values before inhalation were -2.8 after 5 minutes, -7.5 after 10 minutes, -11.2 after 15 minutes, -15.4 after 20 minutes, and -12.6 after 30 minutes. In healthy women inhaled porcaterol and oxitropium, percent changes of respiratory airway resistance compared with values before inhalation were -14.5 after 5 minutes, -18.9 after 10 minutes, -17.0 after 15 minutes, -20.8 after 20 minutes, and -20.4 after 30 minutes. Patterns of decrease of respiratory airway resistance differed between women who have Arg 16/Gly 16 allele (hetero type) and those who have Gly 16/Gly 16 allele (variant type). In women who have Gly 16/Gly 16 allele (variant type), although acute decrease of respiratory airway resistance was observed, the duration of bronchodilator effect by inhaled procaterol and oxitropium was shorter than those observed in Arg 16/Gly 16 allele (hetero type). The present study showed inhalation of procaterol and oxitropium had a differential bronchodilator effect in healthy women, depending on their genotype of beta 2-adrenoceptor polymorphism at codon 16.
有人提出,β2 - 肾上腺素能受体多态性第16密码子处的精氨酸16/甘氨酸16等位基因在下调β2 - 激动剂引起的支气管扩张刺激中起作用。本研究旨在评估健康女性中,第16密码子处具有精氨酸16/甘氨酸16等位基因(杂合型)的人群与具有甘氨酸16/甘氨酸16等位基因(变异型)的人群对β2 - 激动剂(丙卡特罗)和抗胆碱能药物(氧托溴铵)的支气管扩张反应性差异。在吸入丙卡特罗或吸入丙卡特罗和氧托溴铵之前以及之后5、10、15、20和30分钟,通过体容积描记法测量气道阻力和其他肺功能测试指标。在吸入丙卡特罗的健康女性中,与吸入前的值相比,呼吸气道阻力的百分比变化在5分钟后为 -2.8,10分钟后为 -7.5,15分钟后为 -11.2,20分钟后为 -15.4,30分钟后为 -12.6。在吸入丙卡特罗和氧托溴铵的健康女性中,与吸入前的值相比,呼吸气道阻力的百分比变化在5分钟后为 -14.5,10分钟后为 -18.9,15分钟后为 -17.0,20分钟后为 -20.8,30分钟后为 -20.4。具有精氨酸16/甘氨酸16等位基因(杂合型)的女性和具有甘氨酸16/甘氨酸16等位基因(变异型)的女性之间,呼吸气道阻力降低的模式有所不同。在具有甘氨酸16/甘氨酸16等位基因(变异型)的女性中,虽然观察到呼吸气道阻力急性下降,但吸入丙卡特罗和氧托溴铵的支气管扩张作用持续时间比在精氨酸16/甘氨酸16等位基因(杂合型)中观察到的要短。本研究表明,吸入丙卡特罗和氧托溴铵对健康女性具有不同的支气管扩张作用,这取决于她们在第16密码子处的β2 - 肾上腺素能受体多态性基因型。