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正常人和哮喘患者体外淋巴细胞β2-肾上腺素能受体功能参数的比较。

Comparison of parameters of in vitro lymphocyte beta 2-adrenoceptor function in normal and asthmatic subjects.

作者信息

Newnham D M, Coutie W J, McFarlane L C, Lipworth B J

机构信息

Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Scotland, UK.

出版信息

Eur J Clin Pharmacol. 1993;45(6):535-8. doi: 10.1007/BF00315310.

Abstract

There is conflicting data in the literature as to whether subsensitivity of in-vivo beta 2-adrenoceptor (beta 2-AR) responses in patients with asthma is due to an endogenous defect of beta 2-AR or an effect of exogenous beta 2-agonist therapy. The purpose of the study was to compare in-vitro parameters of lymphocyte beta 2-AR function in eight age and sex matched normal [FEV1, 98 (2)% predicted] volunteers and asthmatic [FEV1, 60 (5)% predicted] subjects. The asthmatic group were washed out for 4 weeks by substituting inhaled beta 2-agonist therapy with ipratropium bromide, in order to exclude possible exogenous effects of beta 2-agonist exposure. Receptor binding affinity (Kd) and density (Bmax) were evaluated using (-)125I-iodocyanopindolol and maximal cAMP response (Emax) was assayed following stimulation with isoprenaline (10(-4) M). No significant differences were found between the normal and asthmatic group for Kd (pmol.l-1): 9.65 vs 10.2, Bmax (fmol/10(6) cells): 1.9 vs 1.6, or Emax (pmol/10(6) cells): 4.24 vs 4.85. Thus, parameters of beta 2-AR function are unaltered in asthmatic patients who have not been exposed to beta 2-agonists, suggesting that asthma is not associated with an endogenous defect of beta 2-AR.

摘要

关于哮喘患者体内β2 - 肾上腺素能受体(β2 - AR)反应的亚敏感性是由于β2 - AR的内源性缺陷还是外源性β2 - 激动剂治疗的影响,文献中的数据存在冲突。本研究的目的是比较8名年龄和性别匹配的正常[FEV1,预测值为98(2)%]志愿者和哮喘患者[FEV1,预测值为60(5)%]淋巴细胞β2 - AR功能的体外参数。为了排除β2 - 激动剂暴露可能产生的外源性影响,哮喘组通过用异丙托溴铵替代吸入β2 - 激动剂治疗进行了4周的洗脱。使用(-)125I - 碘氰吲哚洛尔评估受体结合亲和力(Kd)和密度(Bmax),并用异丙肾上腺素(10(-4)M)刺激后测定最大环磷酸腺苷反应(Emax)。正常组和哮喘组之间在Kd(pmol·l-1):9.65对10.2、Bmax(fmol/10(6)个细胞):1.9对1.6或Emax(pmol/10(6)个细胞):4.24对4.85方面未发现显著差异。因此,未接触过β2 - 激动剂的哮喘患者的β2 - AR功能参数未改变,这表明哮喘与β2 - AR的内源性缺陷无关。

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