OXYGEN METABOLITES MODULATE SODIUM-TRANSPORT IN GERBIL MIDDLE-EAR EPITHELIUM - INVOLVEMENT OF PGE(2)

The middle ear epithelium and respiratory epithelia share basic proper ties such as homeostasis of air-filled cavities and mucociliary cleara nce toward the pharynx. With the middle ear SV40-transformed (MESV) ce ll line, we used the short-circuit current (I-sc) technique to investi gate changes in ion transport induced by oxidants. Xanthine and xanthi ne oxidase on the basal side of the monolayers dramatically increased I-sc up to 50%. This effect was not affected by superoxide dismutase o r mannitol, but could be blunted by catalase or 1,3-dimethyl-2-thioure a. Increasing concentrations of H2O2 from 10(-5) to 5 x 10(-4) M produ ced a dose-dependent increase in I-sc from 0.26 +/- 0.16 up to 4.21 +/ - 0.43 mu A/cm(2) (P < 0.05, n = 5). Concentration of half-maximal sti mulation (EC(50)) was 4.68 x 10(-5) M. This effect was inhibited by in domethacin and was related to a sodium transport, since the H2O2-induc ed increase in I-sc could be prevented or abolished by 1) apical addit ion of benzamil (10(-6) M) and 2) substitution of sodium with N-methyl -glucamine. H2O2 exposure also induced indomethacin-sensitive increase in released prostaglandin (PG) E(2) (EC(50) = 5.62 x 10(-5) M) and in cAMP content (EC(50) = 3.95 x 10(-5) M) with similar kinetics. These results suggest that exposure of MESV cells to oxidants stimulates the production of PGE(2), which in turn increases the transepithelial sod ium transport rate.