Oxygen metabolites modulate sodium transport in gerbil middle ear epithelium: involvement of PGE2.
The middle ear epithelium and respiratory epithelia share basic properties such as homeostasis of air-filled cavities and mucociliary clearance toward the pharynx. With the middle ear SV40-transformed (MESV) cell line, we used the short-circuit current (Isc) technique to investigate changes in ion transport induced by oxidants. Xanthine and xanthine oxidase on the basal side of the monolayers dramatically increased Isc up to 50%. This effect was not affected by superoxide dismutase or mannitol, but could be blunted by catalase or 1,3-dimethyl-2-thiourea. Increasing concentrations of H2O2 from 10(-5) to 5 x 10(-4) M produced a dose-dependent increase in Isc from 0.26 +/- 0.16 up to 4.21 +/- 0.43 microA/cm2 (P < 0.05, n = 5). Concentration of half-maximal stimulation (EC50) was 4.68 x 10(-5) M. This effect was inhibited by indomethacin and was related to a sodium transport, since the H2O2-induced increase in Isc could be prevented or abolished by 1) apical addition 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) E2 (EC50 = 5.62 x 10(-5) M) and in cAMP content (EC50 = 3.95 x 10(-5) M) with similar kinetics. These results suggest that exposure of MESV cells to oxidants stimulates the production of PGE2, which in turn increases the transepithelial sodium transport rate.
Herman
P
P
Laboratoire d'Otologie Expérimentale, Faculté Lariboisière-Saint-Louis, Paris.
Tu
T Y
TY
Loiseau
A
A
Clerici
C
C
Cassingena
R
R
Grodet
A
A
Friedlander
G
G
Amiel
C
C
Tran Ba Huy
P
P
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002461:Cell Line, Transformed; D002463:Cell Membrane Permeability / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000502:physiology*; D004432:Ear, Middle / Q000378:metabolism* / Q000648:ultrastructure; D004553:Electric Conductivity; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D005849:Gerbillinae; D005947:Glucose / Q000378:metabolism; D005949:Glucose Oxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008353:Mannitol / Q000378:metabolism; D008854:Microscopy, Electron; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013481:Superoxides / Q000494:pharmacology; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
D017382:Reactive Oxygen Species; D014970:Xanthines; D013481:Superoxides; D019820:Xanthine; D008353:Mannitol; D012964:Sodium; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D005949:Glucose Oxidase; D014969:Xanthine Oxidase; D005947:Glucose; D015232:Dinoprostone