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PMID: 7908880 Published · ppublish English Comparative Study Journal Article

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

European journal of clinical pharmacology ·Vol. 45 ·No. 6 ·1993-00-00 ·Pages 535-8

Newnham DM, Coutie WJ, McFarlane LC, Lipworth BJ

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.

MeSH Terms
Adrenergic beta-Agonists/adverse effects,pharmacokinetics Adult Asthma/metabolism,physiopathology Cyclic AMP/metabolism Female Forced Expiratory Volume/drug effects Humans In Vitro Techniques Iodine Radioisotopes Iodocyanopindolol Isoproterenol/pharmacology Kinetics Lymphocytes/metabolism Male Pindolol/analogs & derivatives Receptors, Adrenergic, beta-2/metabolism Theophylline/pharmacology
Chemicals
Adrenergic beta-Agonists Iodine Radioisotopes Receptors, Adrenergic, beta-2 Iodocyanopindolol Pindolol Theophylline Cyclic AMP Isoproterenol
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Newnham D M
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Scotland, UK.
Coutie W J
McFarlane L C
Lipworth B J
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Article Info
Journal
European journal of clinical pharmacology
Abbr.
Eur J Clin Pharmacol
ISSN
0031-6970
Published
1993-00-00
Pages
535-8
Language
English
Region
Germany
NLM ID
1256165
Subset
IM
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