The effect of trimethoprim on sodium transport across the frog skin epithelium.
Trimethoprim, a dihydrofolate reductase inhibitor, is used as a therapeutical agent in combination with sulfamethoxazole. Studies of the interaction of trimethoprim with membrane transport are rare. This paper presents a study of the effect of trimethoprim on the short-circuit current (Isc) and on the transepithelial total conductance (Gt) of the isolated frog skin. We found a fast drop (less than 1 min) of Isc (50%) and Gt (30%) after the addition of the drug to the outside medium (mucosa). A dose-response curve of the effect of the drug has shown that trimethoprim has no effect for concentrations below 0.01 mM and reaches a half-maximum inhibition at 0.5 mM. Trimethoprim induces a decrease in the sodium radioactive tracer fluxes that parallel the decrease of the observed Isc. It induces a hyperpolarization of the mucosal barrier in the same way that amiloride does. A comparative study of the effect of trimethoprim and amiloride has shown that trimethoprim acts on the amiloride-sensitive sodium channels of the mucosal barrier and behaves as a competitive inhibitor of amiloride with a dissociation constant KTRIM of 53 x 10(-5) M while KAMIL = 46 x 10(-8) M.
Fonseca
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PD
Centro de Tecnologia Química e Biológica (C.T.Q.B.), Laboratory of Biophysics, Oeiras, Portugal.
Moura
T F
TF
Ferreira
K T
KT
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002712:Chlorides / Q000494:pharmacology; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D011895:Rana ridibunda; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012879:Skin Physiological Phenomena; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D012979:Sodium Radioisotopes; D014295:Trimethoprim / Q000494:pharmacology*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology
D002712:Chlorides; D003470:Culture Media; D015222:Sodium Channels; D012979:Sodium Radioisotopes; D000584:Amiloride; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D012964:Sodium; D014295:Trimethoprim