Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aquaporins are known as water channels; however, an additional ion channel function has been observed for several including aquaporin-1 (AQP1). Using primary cultures of rat choroid plexus, a brain tissue that secretes CSF and abundantly expresses AQP1, we confirmed the ion channel function of AQP1 and assessed its functional relevance. The cGMP-gated cationic conductance associated with AQP1 is activated by an endogenous receptor guanylate cyclase for atrial natriuretic peptide (ANP). Fluid transport assays with confluent polarized choroid plexus cultures showed that AQP1 current activation by 4.5 mum ANP decreases the normal basal-to-apical fluid transport in the choroid plexus; conversely, AQP1 block with 500 mum Cd2+ restores fluid transport. The cGMP-gated conductance in the choroid plexus is lost with targeted knockdown of AQP1 by small interfering RNA (siRNA), as confirmed by immunocytochemistry and whole-cell patch electrophysiology of transiently transfected cells identified by enhanced green fluorescent protein. The properties of the current (permeability to Na+, K+, TEA+, and Cs+; voltage insensitivity; and dependence on cGMP) matched properties characterized previously in AQP1-expressing oocytes. Background K+ and Cl- currents in the choroid plexus were dissected from AQP1 currents using Cs-methanesulfonate recording salines; the background currents recorded in physiological salines were not affected by AQP1-siRNA treatment. These results confirm that AQP1 can function as both a water channel and a gated ion channel. The conclusion that the AQP1-associated cation current contributes to modulating CSF production resolves a lingering concern as to whether an aquaporin ionic conductance can have a physiologically relevant function.
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PMID:Ion channel function of aquaporin-1 natively expressed in choroid plexus. 1687 Jul 26

AVP and atrial natriuretic peptide (ANP) have opposite effects in the kidney. AVP induces antidiuresis by insertion of aquaporin-2 (AQP2) water channels into the plasma membrane of collecting duct principal cells. ANP acts as a diuretic factor. An ANP- and nitric oxide (NO)/soluble guanylate cyclase (sGC)-induced insertion of AQP2 into the plasma membrane is reported from different models. However, functional data on the insertion of AQP2 is missing. We used primary cultured inner medullary collecting duct (IMCD) cells and digital holographic microscopy, calcein-quenching measurements, and immunofluorescence and Western blotting to analyze the effects of ANP and NO donors on AQP2 phosphorylation, membrane expression, and water permeability. While AVP led to acceleration in osmotically induced swelling, ANP had no effect. However, in AVP-pretreated cells ANP significantly decreased the kinetics of cell swelling. This effect was mimicked by 8-bromo-cGMP and blunted by PKG inhibition. Stimulation of the NO/sGC pathway or direct activation of sGC with BAY 58-2667 had similar effects to ANP. In cells treated with AVP, AQP2 was predominantly localized in the plasma membrane, and after additional incubation with ANP AQP2 was mostly localized in the cytosol, indicating an increased retrieval of AQP2 from the plasma membrane by ANP. Western blot analysis showed that ANP was able to reduce AVP-induced phosphorylation of AQP2 at position S256. In conclusion, we show that the diuretic action of ANP or NO in the IMCD involves a decreased localization of AQP2 in the plasma membrane which is mediated by cGMP and PKG.
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PMID:Atrial natriuretic peptide and nitric oxide signaling antagonizes vasopressin-mediated water permeability in inner medullary collecting duct cells. 1957 Aug 84