title: Responses of distal nephron Na+transporters to acute volume depletion and hyperkalemia.
abstract: We assessed effects of acute volume reductions induced by administration of diuretics in rats. Direct block of Na+transport produced changes in urinary electrolyte excretion. Adaptations to these effects appeared as alterations in the expression of protein for the distal nephron Na+transporters NCC and ENaC. Two hours after a single injection of furosemide (6 mg/kg) or hydrochlorothiazide (HCTZ; 30 mg/kg) Na+and K+excretion increased but no changes in the content of activated forms of NCC (phosphorylated on residue T53) or ENaC (cleaved γ-subunit) were detected. In contrast, amiloride (0.6 mg/kg) evoked a similar natriuresis that coincided with decreased pT53NCC and increased cleaved γENaC. Alterations in posttranslational membrane protein processing correlated with an increase in plasma K+of 0.6-0.8 mM. Decreased pT53NCC occurred within 1 h after amiloride injection, whereas changes in γENaC were slower and were blocked by the mineralocorticoid receptor antagonist spironolactone. Increased γENaC cleavage correlated with elevation of the surface expression of the subunit as assessed by in situ biotinylation. Na depletion induced by 2 h of furosemide or HCTZ treatment increases total NCC expression without affecting ENaC protein. However, restriction of Na intake for 10 h (during the day) or 18 h (overnight) increased the abundance of both total NCC and of cleaved α- and γENaC. We conclude that the kidneys respond acutely to hyperkalemic challenges by decreasing the activity of NCC while increasing that of ENaC. They respond to hypovolemia more slowly, increasing Na+reabsorptive capacities of both of these transporters.
authors.affiliation: Department of Physiology and Biophysics, Weill-Cornell Medical College, New York, New York.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Frindt
authors.affiliation: Department of Physiology and Biophysics, Weill-Cornell Medical College, New York, New York.|Department of Physiology, Harbin University School of Medicine, Harbin, China; and.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Department of Physiology and Biophysics, Weill-Cornell Medical College, New York, New York.|Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Weinstein
authors.affiliation: Department of Physiology and Biophysics, Weill-Cornell Medical College, New York, New York; lgpalm@med.cornell.edu.
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Palmer
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D004232:Diuretics / Q000494:pharmacology* / Q000633:toxicity; D053503:Epithelial Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D006947:Hyperkalemia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism* / Q000652:urine; D020896:Hypovolemia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism* / Q000652:urine; D008297:Male; D008954:Models, Biological; D009399:Nephrons / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D011188:Potassium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D017207:Rats, Sprague-Dawley; D065667:Renal Elimination / Q000187:drug effects; D012964:Sodium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D064486:Solute Carrier Family 12, Member 3 / Q000187:drug effects / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D004232:Diuretics; D053503:Epithelial Sodium Channels; C507054:Scnn1g protein, rat; C578876:Slc12a3 protein, rat; D064486:Solute Carrier Family 12, Member 3; D006852:Hydrochlorothiazide; D013148:Spironolactone; D000584:Amiloride; D005665:Furosemide; D012964:Sodium; D011188:Potassium
keywords: ENaC; NCC; amiloride; furosemide; hydrochlorothiazide; hyperkalemia