title: Metabolic acid-base influences on renal thiazide receptor density.
abstract: The renal responses to metabolic acidosis/alkalosis involve changes in the proximal tubule, loop of Henle, and collecting ducts. We tested for acid- or base-induced changes in the distal convoluted tubule (DCT) by examining the renal density of the DCT's receptor for thiazide-type diuretics (TZR), as estimated by the binding of [3H]metolazone in Wistar-Kyoto rats. TZR density significantly decreased by 17% in rats ingesting NH4Cl for 3.5 days and by nearly 30% after 7 days; TZR increased up to 40% in rats ingesting NaHCO3 for 2-4 days but was no longer significantly increased after 7 days. Urinary excretion of chloride increased as renal density of the TZR decreased, a finding consistent with the interpretation that acidosis/alkalosis not only altered TZR density but coordinately altered reabsorption of NaCl by the thiazidesensitive Na-Cl cotransporter. The result is that delivery of Na from DCT is enhanced during acidosis and decreased during alkalosis, assisting in compensatory changes in distal nephron secretion of hydrogen ion. The integrated renal response to metabolic acidosis/alkalosis involves a decrease in renal TZR with acidosis and an increase in TZR with alkalosis.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla 92093-0623, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Fanestil
authors.forename: D A
authors.initials: DA
authors.lastname: Vaughn
authors.forename: P
authors.initials: P
authors.lastname: Blakely
mesh_terms: D000136:Acid-Base Equilibrium; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000378:metabolism*; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D011955:Receptors, Drug / Q000378:metabolism*; D012727:Sex Characteristics; D017693:Sodium Bicarbonate / Q000008:administration & dosage / Q000494:pharmacology; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D011955:Receptors, Drug; C578876:Slc12a3 protein, rat; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor; D000643:Ammonium Chloride; D017693:Sodium Bicarbonate