title: Active NH4+ absorption by the thick ascending limb.
abstract: Isolated perfused medullary thick ascending limbs from rabbits were studied to determine the mechanism of ammonium ion absorption. Under control conditions, thick ascending limbs spontaneously absorbed NH4+ and generated a lumen-positive potential. When these tubules were chemically voltage clamped to lumen-negative potentials by lowering the bath NaCl concentration, NH4+ absorption persisted. Thus NH4+ was absorbed against an electrochemical gradient. The active flux accounts for most of the net flux under control conditions, the remainder being due to passive paracellular NH4+ diffusion. The NH4+ permeability, measured in separate experiments, was high (1.50 +/- 0.25 x 10(-4) cm/s) compared with values in other segments. The NH3 permeability was relatively low (3.1 +/- 0.5 x 10(-3) cm/s). Luminal furosemide (10(-4) M) eliminated most of the active NH4+ flux, indicating that a major fraction of the active flux is dependent on apical entry of NH4+ via the Na+ -K+ -2Cl- cotransporter (presumably by substitution for K+). The remaining active flux was completely inhibited by 10(-4) M ouabain in the bath. Active chloride absorption was maintained when NH4+ entirely replaced K+ in bath and perfusate, indicating that NH4+ substitutes for K+ on the apical cotransporter and the basolateral Na+ -K+ -ATPase. Ammonium absorption provides an active "single effect" for countercurrent multiplication of NH4+ in the renal medulla.
authors.affiliation: Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.
authors.forename: J L
authors.initials: JL
authors.lastname: Garvin
authors.forename: M B
authors.initials: MB
authors.lastname: Burg
authors.forename: M A
authors.initials: MA
authors.lastname: Knepper
mesh_terms: D000042:Absorption; D000465:Algorithms; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D002712:Chlorides / Q000378:metabolism; D005665:Furosemide / Q000494:pharmacology; D007679:Kidney Medulla / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D010539:Permeability; D011817:Rabbits
chemical_list: D002712:Chlorides; D010042:Ouabain; D000641:Ammonia; D005665:Furosemide