THE HUMAN BRONCHUS MODEL IN-VITRO - PHARMACOLOGICAL APPROACH OF VARIOUS COMPONENTS INVOLVED IN THE FUNCTIONAL-RESPONSE

Studying the human bronchi in vitro, and therefore sheltered from the toxicity problems inherent in human experiments, makes it possible to conduct a monofactorial analysis, disregarding the perturbations engen dered by reflex phenomena, hemodynamic changes, etc. Analysing the eff ects of mediators on tissues may be less simple that it looks, due to the multiplicity of the cell types that are present. For example, in s tudying the effects of bradykinin we have shown that bradykinin is a p otent contractile agent of small-diameter isolated bronchi, whereas it has no significant contractile effect on larger bronchi. The bradykin in-induced contraction results from a contractile component due to sti mulation of the TP receptor, and of a relaxant component due to relaxa nt prostanoids. The two components of the bradykinin effects are produ ced by stimulation of B-2 receptors. In vitro stimulation of bronchi b y LPS or interleukin-1 beta permits us to obtain hyperreactivity to br adykinin due to induction of thromboxane synthetase or isomerase rathe r than to induction of B-2 receptors or cyclooxygenase. Involvement of the nervous system may persist in the in vitro bronchial model, and i ndeed we have shown, for example, that pentamidine, well known for its tussigenic effect, is an indirect parasympathomimetic compound. Thus, study of the isolated bronchus permits an approach to the mechanisms of action of medicinal drugs. Despite the simplification provided comp ared to the in vivo study, analysis of bronchoreactivity on the isolat ed bronchus must take into account numerous parameters which interfere with the proper effects of the substances.