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)

Endothelium-derived relaxing factor (EDRF) activates soluble guanylate cyclase, resulting in an increase in vascular smooth muscle guanosine 3',5'-cyclic monophosphate (cGMP) levels, which correlates with its relaxing effect. Using a microdialysis technique, we investigated changes in right and left renal interstitial fluid cGMP levels in response to right intrarenal administration of an EDRF inhibitor, NG-monomethyl-L-arginine (L-NMMA). Studies were conducted in anesthetized dogs (n = 5) in metabolic balance at a sodium intake of 40 meq/day. Urine was collected directly from the right and left ureters individually. Changes in the right and left urinary cGMP excretion and renal function in response to cumulative doses of L-NMMA were studied. In the right kidney, 20-100 micrograms/kg/min L-NMMA caused 1) a dose-dependent decrease in renal interstitial fluid and urinary cGMP levels (p less than 0.0001 and p less than 0.001, respectively), 2) antinatriuresis (p less than 0.01), 3) antidiuresis (p less than 0.01), 4) a decrease in renal blood flow (p less than 0.01) and glomerular filtration rate (p less than 0.01), and 5) a decrease in fractional sodium excretion (p less than 0.01). No changes in left renal interstitial fluid and urinary cGMP levels or excretory and hemodynamic function were observed during right intrarenal administration of L-NMMA at 20 and 60 micrograms/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide alters renal function and guanosine 3',5'-cyclic monophosphate. 131 56

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