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)

Urinary excretion of renal brush border enzymes may serve as an early marker of renal injury. However, the distinction between physiological and pathological levels remains controversial, since enzymuria is affected by physiological parameters. To clarify the influence of diuresis, we investigated the urinary excretion of alanine-aminopeptidase (AAP; EC 3.4.11.2) as function of diuretic state. 17 healthy volunteers of both sexes were subjected to protocols with sudden or prolonged water load preceded and followed by a thirst period. Urinary excretion of AAP was measured using an enzyme kinetic assay. As expected AAP excretion increased with urine flow, the increments diminished yielding an overall excretion pattern that resembled saturation kinetics. This function is described by a mathematical model. This model assumes, that AAP is released in proximal tubules at a constant rate and reabsorbed or inactivated in the distal tubule and collecting duct. Non-linear fits of the model equation to our data allowed two parameters, chi and mu, to be defined. Chi describes the rate of AAP release independent of urinary flow, and mu the ratio of distal tubular reabsorption or inactivation. If a substrate is not reabsorbed at all, mu approximates zero. Since mu fitted for AAP differed significantly from zero, this indicates reabsorption or inactivation of AAP in the distal nephron. Therefore, our study supports the theory of flow-dependent reabsorption or inactivation of AAP in the distal nephron.
 ...
PMID:Influence of diuresis on enzymuria. 1149 53

Congenital nephrogenic diabetes insipidus (NDI) is characterized by the inability of the kidney to concentrate urine. Congenital NDI is mainly caused by loss-of-function mutations in the vasopressin type 2 receptor (V2R), leading to impaired aquaporin-2 (AQP2) water channel activity. So far, treatment options of congenital NDI either by rescuing mutant V2R with chemical chaperones or by elevating cyclic adenosine monophosphate (cAMP) levels have failed to yield effective therapies. Here we show that inhibition of A-kinase anchoring proteins (AKAPs) binding to PKA increases PKA activity and activates AQP2 channels in cortical collecting duct cells. In vivo, the low molecular weight compound 3,3'-diamino-4,4'-dihydroxydiphenylmethane (FMP-API-1) and its derivatives increase AQP2 activity to the same extent as vasopressin, and increase urine osmolality in the context of V2R inhibition. We therefore suggest that FMP-API-1 may constitute a promising lead compound for the treatment of congenital NDI caused by V2R mutations.
 ...
PMID:AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus. 2965 Sep 69