Effect of Furosemide on Prostaglandin Synthesis by Human Nasal and Bronchial Epithelial Cells in Culture

Inhaled furosemide protects asthmatic subjects against bronchial obstruction caused by indirect provocants. We have attempted to correlate the protective effect of furosemide with its ability to alter prostaglandin (PG) synthesis by the airway epithelium. Human epithelial cells from nasal polyps and bronchi were cultured in DME-Ham's F12 medium with 10% fetal calf serum. Confluent cells (days 6 through 8) were incubated for 30 min in fresh medium, and the PGs in the supernatant were measured by radioimmunoassay. Spontaneous output (ng.ml-1.mg-1 cell protein) was as follows (mean +/- SEM): PGE2 = 7.74 +/- 2.10 (n = 12), PGF2 alpha = 1.66 +/- 0.12 (n = 15), 6-keto-PGF1 alpha = 4.32 +/- 1.37 (n = 11), PGD2 = 0.73 +/- 0.16 (n = 11) for bronchial cells and PGE2 = 7.24 +/- 0.80 (n = 32), PGF2 alpha = 1.38 +/- 0.12 (n = 17), 6-keto-PGF1 alpha = 6.79 +/- 2.50 (n = 15), PGD2 = 0.42 +/- 0.07 (n = 17) for nasal cells. Incubation with arachidonic acid (25 micrograms/ml) for 30 min significantly increased the amounts of the four PGs. Incubation with furosemide (10(-4) M) for 30 min caused a marked reduction in both basal and arachidonic acid-stimulated production of PGE2 and PGF2 alpha but did not reduce production of 6-keto-PGF1 alpha and PGD2. Incubation with bumetanide (10(-4) M) for 30 min did not modify the PGE2 synthesis by nasal epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)