Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tubular acidosis is diagnosed when hyperchloremic acidosis is associated with inappropriate NH4 excretion (less than or equal to 40 mmol/24 hours). Urinary pH is variable because it depends on the secretion of H+ into the collecting duct and is inversely correlated with the amount of ammonia available in the urine. Administration of NaHCO3 for diagnostic purpose allows to eliminate proximal tubular acidosis and to measure the elevation of urinary PCO2 reflecting the secretion of H+ in the collecting duct. Hypokalemia points towards distal tubular acidosis, either by defect of H(+)-ATPases pumps, or by the incapacity to create a normal gradient of H+. In contrast hyperkalemia suggests distal tubular acidosis associated either with hypoaldosteronism or with diminution of trans-epithelial voltage or with pseudohypoaldosteronism. The incidence of distal tubular acidosis with hyperkalemia is increasing whereas distal tubular acidosis with hypokalemia remain rare.
 ...
PMID:[Distal tubular acidosis. Recent data]. 165 91

The human SLC4A5 gene has been identified as a hypertension susceptibility gene based on the association of single nucleotide polymorphisms with blood pressure (BP) levels and hypertension status. The biochemical basis of this association is unknown particularly since no single gene variant was linked to hypertension in humans. SLC4A5 (NBCe2, NBC4) is expressed in the collecting duct of the kidney and acts as an electrogenic ion-transporter that transports sodium and bicarbonate with a 1:2 or 1:3 stoichiometry allowing bicarbonate reabsorption with relatively minor concurrent sodium uptake. We have mutated the Slc4a5 gene in mice, which caused a persistent increase in systolic and diastolic BP. Slc4a5 mutant mice also displayed a compensated metabolic acidosis and hyporeninemic hypoaldosteronism. Analysis of kidney physiology revealed elevated fluid intake and urine excretion and increased glomerular filtration rate. Transcriptome analysis uncovers possible compensatory mechanisms induced by SLC4A5 mutation, including upregulation of SLC4A7 and pendrin as well as molecular mechanisms associated with hypertension. Induction of metabolic alkalosis eliminated the BP difference between wild-type and Slc4a5 mutant mice. We conclude that the impairment of the function of SLC4A5 favors development of a hypertensive state. We reason that the loss of sodium-sparing bicarbonate reabsorption by SLC4A5 initiates a regulatory cascade consisting of compensatory bicarbonate reabsorption via other sodium-bicarbonate transporters (e.g. SLC4A7) at the expense of an increased sodium uptake. This will ultimately raise BP and cause hypoaldosteronism, thus providing a mechanistic explanation for the linkage of the SLC4A5 locus to hypertension in humans.
 ...
PMID:Targeted mutation of SLC4A5 induces arterial hypertension and renal metabolic acidosis. 2208 31