Abstract
The hypothesis was tested that endogenous leukotriene (LT) production in the lung causes desensitisation of airway smooth muscle to LT. The synthesis of LTB 4, C 4, D 4 and E 4 by human lung tissue, obtained at thoracotomies, after stimulation with Ca-ionophore was assessed by HPLC. Functional studies of small airway smooth muscle from the same tissue specimens were carried out using LTC 4 and methacholine as the contracting agents. Generation of LTB 4, C 4, D 4 and E 4 was 453 ± 82, 84 ± 15, 71 ± 27 and 40 ± 16 pmol/g fresh tissue respectively (mean ± S.E.M., n = 10). All airway smooth muscle preparations responded to LTC 4 in a concentration dependent way with a −log EC 20 of 8.56 ± 0.13, a −log EC 50 of 7.95 ± 0.08 and a T max of 82 ± 11 mg force/mg tissue weight, corresponding to 79 ± 4% of the maximal response to methacholine (mean ± S.E.M.; 27 preparations from 10 patients). No correlations were found between any of the functional parameters (−logEC 20, −logEC 50, T max to LTC 4 and methacholine) and the amounts of LT's generated by the lung tissue. Furthermore airway smooth muscle contractility was not significantly reduced after repeated exposure of bronchiolar strips to LTC 4 in vitro. These findings suggest that the responsiveness of human peripheral airway smooth muscle to LT is not related to the capacity of the lung tissue to synthetize LT.
Published Version
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