Comparison of parameters of in vitro lymphocyte beta 2-adrenoceptor function in normal and asthmatic subjects.
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.
Newnham
D M
DM
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Scotland, UK.
Coutie
W J
WJ
McFarlane
L C
LC
Lipworth
B J
BJ
D000318:Adrenergic beta-Agonists / Q000009:adverse effects* / Q000493:pharmacokinetics; D000328:Adult; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D007457:Iodine Radioisotopes; D018343:Receptors, Adrenergic, beta-2; D020120:Iodocyanopindolol; D010869:Pindolol; D013806:Theophylline; D000242:Cyclic AMP; D007545:Isoproterenol