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Continued exposure of target cells to a hormonal agonist frequently leads to a blunted response to that agonist. This process has been termed desensitization, refractoriness, tolerance or tachyphylaxis. The receptor involved in case of beta-sympathomimetics is the beta-adrenergic receptor. When the clinical aspects of beta-adrenergic receptor desensitization are considered, a number of points need serious attention: 1) the route of administration of the drug and the concentration of the drug reached at the receptor site; 2) other factors which may cause reduced responsiveness of the beta-adrenergic receptor besides beta-sympathomimetics and interfere with this process; 3) the different cell-types which are studied and thought to be representative for processes taking place at lung tissue level; 4) the in vivo parameter(s) chosen to describe desensitization; 5) the difference between normal and asthmatic subjects; 6) the mechanism behind desensitization. The paper concerns a review of these points. Since the clinical findings with respect to the induction of desensitization by beta-sympathomimetics are rather controversial, the therapeutic advice should be: use it with caution.

In eight asthmatic and six normal subjects serum terbutaline concentrations were correlated with changes in FEV1, MEF50%, Gaw, sGaw, and plasma cAMP concentrations after administration of 0.5 mg terbutaline subcutaneously, 5 mg orally, and an oral placebo. In asthmatics and normals the changes in serum terbutaline levels and plasma cAMP levels were closely correlated and in the same range. No change in lung function parameters was registered in normals, whereas in asthmatics a significant improvement was shown. In asthmatics all lung function parameters closely parallelled the changes in serum terbutaline concentrations and cAMP plasma concentrations, the FEV1 being the least variable lung function parameter. The maximal effect in FEV1 occurred 30-60 min after the subcutaneous dose and 2-4 h after the oral dose. The FEV1 improvement showed a linear relationship with the serum terbutaline concentration between 1.6 and 6 ng/ml. In contrast with theophyllines and anticholinergics, serum terbutaline concentrations showed a very low interindividual variance. Nevertheless it appeared that prediction of a certain improvement in lung function was not possible on the basis of the serum concentration. Since changes in plasma cAMP values after terbutaline therapy were similar in normals and asthmatics, the lung function improvement in the asthmatics suggests that if a beta-adrenergic defect exists, this must be mainly situated in the lung tissue.