title: The use of a diuretic agent as a probe to investigate site and mechanism of ion transport processes.
abstract: Several features emerge from consideration of a furosemide-sensitive cotransport mechanism in the various tissues surveyed. First discovered in epithelia, above all in the kidney because of its potent diuretic effect, furosemide inhibits a cotransport mechanism that tightly couples the movement of sodium, chloride and potassium. Its mode of operation is electrically neutral and in all tissues so far examined, the cotransport-mediated ion movement is driven by the electrochemical potential of the cotransported ion-species. The energy for this ion movement derives ultimately from the Na-K pump that establishes the Na gradient that drives the coupled ion movement. This type of carrier-mediated and ion-specific solute movement expands the traditional "pump-leak" model of cellular ion transport by providing dissipative "leak" pathways in addition to the well-established ion channels that allow solute movement by electrodiffusion. An important feature of the cotransport mechanism is its important role in both reabsorptive and secretory epithelial transport operations. This variability can be adequately explained by the location of the cotransport mechanism in either the apical or basolateral cell membrane of such epithelia as the renal tubule, the intestinal mucosa, the rectal gland or the trachea. In addition, the furosemide-sensitive transporter has also been shown to play a significant role in cell volume regulation, both in epithelia and in non-epithelia cells, and it appears to participate in the regulation of the cell chloride concentrations in excitable tissues.
authors.forename: G
authors.initials: G
authors.lastname: Giebisch
mesh_terms: D000818:Animals; D001692:Biological Transport; D001693:Biological Transport, Active; D002712:Chlorides / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005665:Furosemide; D007473:Ion Channels / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D011188:Potassium / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
chemical_list: D002712:Chlorides; D007473:Ion Channels; D005665:Furosemide; D012964:Sodium; D011188:Potassium