EFFECT OF FUROSEMIDE ON PROSTAGLANDIN SYNTHESIS BY HUMAN NASAL AND BRONCHIAL EPITHELIAL-CELLS IN CULTURE

Inhaled furosemide protects asthmatic subjects against bronchial obstr uction caused by indirect provocants. We have attempted to correlate t he protective effect of furosemide with its ability to alter prostagla ndin (PG) synthesis by the airway epithelium. Human epithelial cells f rom nasal polyps and bronchi were cultured in DME-Ham's F12 medium wit h 10% fetal calf serum. Confluent cells (days 6 through 8) were incuba ted for 30 min in fresh medium, and the PGs in the supernatant were me asured by radioimmunoassay. say. Spontaneous output (ng.ml(-1).mg(-1) cell protein) ws follows (mean +/- SEM): PGE(2) = 7.74 +/- 2.10 (n = 1 2), PGF(2 alpha) = 1.66 +/- 0.12 (n = 15), 6-keto-PGF(1 alpha) = 4.32 +/- 1.37 (n = 11), PGD(2) = 0.73 +/- 0.16 (n = 11) for bronchial cells and PGE(2) = 7.24 +/- 0.80 (n = 32), PGF(2a) = 1.38 +/- 0.12 (n = 17) , 6-keto-PGF(1 alpha) = 6.79 +/- 2.50 (n = 15), PGD(2) = 0.42 +/- 0.07 (n = 17) for nasal cells. Incubation with arachidonic acid (25 mu/ml) for 30 min significantly increased the amounts of the four PGs. Incub ation with furosemide (10(-4) M) for 30 min caused a marked reduction in both basal and arachidonic acid-stimulated production of PGE(2) and PGF(2 alpha) but did not reduce production of 6-keto-PGF(1 alpha) and PGD(2). Incubation with bumetanide (10(-4) M) for 30 min did not modi fy the PGE(2) synthesis by nasal epithelial cells. The differential ef fects of furosemide on PG production by primary cultures of human airw ay epithelial cells might be best explained by inhibition of PGH-9-ket o-isomerase and PGH-PGF(2 alpha) reductase. Because PGE(2) potentiates the effects of inflammatory mediators in airways through its vasodila tor effect on the tracheobronchial circulation, and because PGF(2 alph a) is a mild bronchoconstrictor agent, our results suggest that inhale d furosemide might protect asthmatic subjects against indirect provoca nts by decreasing the production of these PGs by airway epithelial cel ls.