Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple cationic channels with variable selectivity for Ca(2+) , K(+) and Na(+) have been identified in smooth muscle cells (SMC) as well as non-excitable cells. They control Ca(2+) store refilling and depletion, G-protein-mediated receptor activation, apoptosis and cell growth, membrane potential, intracellular pH, oxidative stress, phospholipid signaling, and other critical cell functions. A novel superfamily of divalent cation channels has been recently characterized as highly conserved heterotetramer homologues of Drosophila transient receptor potential (TRP). At least 50 members of seven major TRP channel families have been identified to date. The involvement of TRP in store-operated Ca(2+) - gating has been demonstrated in various tissues, along with intestinal and renal epithelial cell Ca(2+) and Mg(2+) transport, indicating a role in total body homeostasis of divalent cations. TRPV5-null mice display phenotypic defects including hypercalciuria and impaired bone mineral density. TRPP2 or polycystin 2 (PC2), encoded by the PKD2 gene, is an integral protein of epithelial cilia whose mutation is associated with autosomal dominant polycystic kidney disease (ADPKD). A TRPP1 (polycystin 1)-PC2 channel complex is actually implicated in the transduction of environmental signals (i.e. luminal tubular fluid flow and composition) into cellular events, such as epithelial cell growth. TRP channels can eventually play a role in the pathogenesis of arterial hypertension via direct effects on vascular smooth muscle contraction, renal blood flow, glomerular hemodynamics and the tubular handling of Ca(2+) and electrolytes.
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PMID:Transient receptor potential channels in the kidney: calcium signaling, transport and beyond. 1652 21

The Drosophila trp homologue Transient Receptor Potential (TRP) cation channels are ubiquitous in most species and cell types. The functional TRP subclasses TRPC, TRPV and TRPP gate Ca2+ and other cations in mammalian tissues, including the kidney. It is now clear that TRP channels play an important role in renal physiology and in certain genetic disorders of the kidney. Hence, there is considerable interest in targeting mutated or dysfunctional TRP channels in an effort to treat such diseases. Transcellular epithelial cell Ca2+ reabsorption occurs in the distal tubule via luminal TRPV5/V6 channels. Indeed, TRPV5 KO mice display phenotypic defects of renal disease, including hypercalciuria and impaired bone mineral density. Similar to Ca2+, Mg2+ transcellular reabsorption occurs in the distal convoluted tubule via apical TRPM6/TRPM7 channels. TRPC6 is a component of the glomerular podocyte "slit diaphragm" and its autosomic dominant mutation has been linked to a familial, steroid-resistant form of nephrotic syndrome. A more common inherited disorder of the tubular epithelium, autosomal dominant polycystic kidney disease (ADPKD), is at least in part related to mutation of polycystin 2 (PC2), a protein encoded by the PKD2 gene. PC2 is now identified as TRPP2, a Ca(2+)-permeable non-selective cation channel located on the cilia of tubular epithelial cells. TRP-related ion transport may also play a role in the pathogenesis of arterial systemic and/or pulmonary hypertension through regulation of vascular smooth muscle contraction, renal perfusion/hemodynamics, as well as the total body balance of divalent cations. Thus, multiple renal TRP channels are potential targets for pharmacological intervention aimed at preventing or attenuating the burden of chronic kidney disease.
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PMID:TRP channels as therapeutic targets in kidney disease and hypertension. 2343 67