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Articles in PresS, published online ahead of print November 20, 2001
Am J Physiol Renal Physiol, 10.1152/ajprenal.00284.2001
Submitted on September 13, 2001
Accepted on November 14, 2001
1 Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, UNAM, Tlalpan, Mexico City, Mexico; Molecular Physiology Unit, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico City, Mexico
2 Molecular Physiology Unit, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico City, Mexico; Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, UNAM, Tlalpan, Mexico City, Mexico
3 Departmento de Bioquimica, Facultad de Quimica, UNAM, Coyoacan, Mexico City, Mexico
* To whom correspondence should be addressed. E-mail: gamba{at}mailer.main.conacyt.mx.
The purpose of the present study was to determine the major functional, pharmacological and regulatory properties of the flounder thiazide-sensitive Na-Cl cotransporter (flTSC), to make a direct comparison with our recent characterization of the rat TSC (rTSC) (Monroy et al. Am. J Physiol Renal Physiol 279:F161-F169, 2000). When expressed in Xenopus laevis oocytes, flTSC exhibits lower affinity for Na+ than for Cl-, with apparent Km of 58.2 ± 7.1 mM and 22.1 ± 4.2 mM, respectively. These Km values are significantly higher than those observed in rTSC. The Na+ and Cl- affinities decreased when the concentration of the counterion was lowered, suggesting that the binding of one ion increases the affinity of the transporter for the other. The effect of several thiazides upon flTSC function was biphasic. Low concentrations of thiazides (10-9 to 10-7 M) resulted in activation of the cotransporter, whereas higher concentrations (10-6 to 10-4 M) were inhibitory. In rTSC, this biphasic effect was observed only with chlortalidone. The affinity for thiazides in flTSC was lower than in rTSC, but the affinity in flTSC was not affected by the Na+ or the Cl- concentration in the uptake medium. In addition to thiazides, flTSC and rTSC were inhibited by mercury, with an apparent higher affinity for rTSC. Finally, flTSC function was decreased by activation of the protein kinase C with phorbol esters and by hypertonicity. In summary, we have found significant regulatory, kinetic, and pharmacological differences between the flounder and rat TSC orthologues.
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