Abstract

Histamine concentration-effect curves were obtained using either an individual or cumulative dosing method. The maximal response to histamine in bronchial preparations using the individual dosing protocol was 0.25 +/- 0.03 g/mm2 and similar results were obtained using the cumulative method (0.24 +/- 0.03 g/mm2). The sensitivity (pD2 value) of isolated human bronchial muscle preparations was comparable for both the individual and cumulative methods (5.71 and 5.16, respectively). Prostaglandin (PG) E2 and PGF2 alpha contracted isolated human bronchial muscle preparations and the pD2 values were 5.64 and 5.59, respectively. PGE2 did not relax bronchial muscle preparations contracted with histamine (50 microM). At high concentrations prostacyclin (3 microM) relaxed histamine-contracted bronchial tissues but this effect was quite variable. Indomethacin (1.7 microM) did not affect basal tone in bronchial tissues. Isolated human bronchial preparations which were contracted maximally with histamine always released measurable quantities of PGs. In some experiments the rat stomach strip was used to detect the presence of these substances before and subsequent to the indomethacin (1.7 microM) treatment. The use of radioimmunoassay for PGE2 and PGF2 alpha confirmed these bioassay results. In a large number of experiments (18 preparations from 9 individual lung samples) the baseline production of PGs was PGE2, 22.9 +/- 2.8 pg/mg of tissue and PGF2 alpha, 11.9 +/- 2.5 pg/mg of tissue. Subsequent to histamine stimulation the quantities of PGs released were PGE2, 72.4 +/- 7.6 pg/mg of tissue and PGF2 alpha, 40.9 +/- 7.3 pg/mg of tissue.(ABSTRACT TRUNCATED AT 250 WORDS)