Temperature Dependence Suggests Multiple Transepithelial Transport Pathways for Urea and Na + in Isolated Perfused Thin Limbs of Henle's Loops

Abstract

Development of urea transport inhibitors as clinically useful diuretics requires precise understanding of urea transepithelial transport in all nephron segments. Urea and Na+ transepithelial permeabilities in rat inner medullary thin limbs of Henle's loops are very high; however, pathways for urea and Na+ fluxes are unknown. Inner medullary thin limbs include the upper descending thin limb (upper DTL), which is AQP1-positive, lower descending thin limb (lower DTL), which is AQP1-negative and ascending thin limb (ATL). When measured at 37° C and 16° C, urea permeabilities of isolated perfused upper DTLs are unchanged (~50 E-5 cm/s); however, at 16° C urea permeabilities in lower DTLs are significantly and reversibly reduced from their values at 37° C by about 33% (from ~420 E-5 cm/s to about 280 E-5 cm/s). Qualitatively identical temperature effects are seen for transepithelial Na+ permeabilities in thin limb segments. At least two transepithelial pathways may account for urea and Na+ fluxes in thin limbs of Henle's loops – one temperature dependent and one temperature independent. Pathway differences may depend on a combination of carrier-mediated transport and/or gating of channels.