Effects of bumetanide on chloride transport in human eccrine sweat ducts: implications for cystic fibrosis.
The effect of the loop diuretic bumetanide on Cl- transport in the human reabsorptive sweat duct (RSD) was studied to determine the properties of Cl- transport in this tissue with an emphasis on its role in cystic fibrosis. Bumetanide (10(-4) M) in the bath decreased the NaCl reabsorption rate (+/- SE) from 235 +/- 72 to 77 +/- 24 pmol/min per mm (n = 10). Bumetanide in the lumen decreased the rate of NaCl reabsorption to a lesser extent from 132 +/- 17 to 84 +/- 16 pmol/min per mm (n = 9). At least part of this inhibition appears to be due to the inhibition of a Cl- conductance in the RSD, as evidenced by a significant increase in the specific resistance (Rt) of the tissue from 8.3 +/- 0.6 to 52.7 +/- 19.3 omega/cm2(n = 3) due to bumetanide in the bath. Luminal bumetanide also increased Rt but to a lesser degree [from 9.8 +/- 1.2 to 16.4 +/- 2.0 omega/cm2 (n = 3)]. Bumetanide also affected the transepithelial potential (Vt), hyperpolarizing it from -10.9 +/- 0.8 to -28.6 +/- 2.0 mV (n = 13). In ouabain-inhibited ducts, a threefold dilution of luminal NaCl concentration resulted in a -13.5 +/- 1.7 mV dilution diffusion potential which was abolished by bumetanide in the bath, indicating that bumetanide removed the anion selectivity of the epithelium. Bumetanide hyperpolarized the basolateral membrane potential (Vb) from -33.6 +/- 1.9 to -44.3 +/- 1.4 mV and depolarized the apical membrane potential (Va) from -20.9 +/- 0.9 to 14.0 +/- 1.3 mV. These results suggest that bumetanide inhibits transcellular Cl- conductance with possible additional effects on the paracellular Cl- conductance pathway as well.
Division of Biomedical Sciences, University of California, Riverside 92521-0121.
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Reddy
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Quinton
D000042:Absorption; D002034:Bumetanide / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology*; D004439:Eccrine Glands / Q000187:drug effects / Q000378:metabolism*; D004848:Epithelium / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D012965:Sodium Chloride / Q000378:metabolism*; D013545:Sweat Glands / Q000378:metabolism*
D004232:Diuretics; D002034:Bumetanide; D012965:Sodium Chloride