Primary Structure and Functional Expression of a Cdna Encoding the Thiazide-Sensitive, Electroneutral Sodium-Chloride Cotransporter GERARDO GAMBA*, SAMUEL N
Proc. Natl. Acad. Sci. USA Vol. 90, pp. 2749-2753, April 1993 Physiology Primary structure and functional expression of a cDNA encoding the thiazide-sensitive, electroneutral sodium-chloride cotransporter GERARDO GAMBA*, SAMUEL N. SALTZBERG*t, MICHAEL LOMBARDI*, AKIHIKO MIYANOSHITA*, JONATHAN LYTTON*, MATTHIAS A. HEDIGER*, BARRY M. BRENNER*, AND STEVEN C. HEBERT*t§ *Laboratory of Molecular Physiology and Biophysics, Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Center for Study of Kidney Disease, Harvard Medical School, 75 Francis Street, Boston, MA 02115; and tMount Desert Island Biological Laboratory, Salsbury Cave, ME 04672 Communicated by Robert W. Berliner, December 17, 1992 ABSTRACT Electroneutral Na+:Cl- cotransport systems et al. (15) have identified a protein band of 185 kDa obtained are involved in a number of important physiological processes from membranes of rabbit renal cortex exposed to [3H]me- including salt absorption and secretion by epithelia and cell tolazone that may be a component of the thiazide-sensitive volume regulation. One group of Na+:Cl- cotransporters is Na+:Cl- cotransporter. specifically inhibited by the benzothiadiazine (thiazide) class of In this report we describe the sequence, functional and diuretic agents and can be distinguished from Na+:K+:2ClI pharmacological characterization, and tissue-specific expres- cotransporters based on a lack of K+ requirement and insen- sion of a cDNA clone (TSCil) encoding the electroneutral sitivity to sulfamoylbenzoic acid diuretics like bumetanide. We thiazide-sensitive Na+ :C1- cotransporter, isolated by a func- report here the isolation of a cDNA encoding a thiazide- tional expression strategy from the urinary bladder of the sensitive, electroneutral sodium-chloride cotransporter from euryhaline teleost P.
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