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)

Recent evidence suggests that nitric oxide (NO) within the inner medullary collecting duct (IMCD) functions to regulate sodium and water reabsorption. Because fluid shear stress has been shown to increase NO production in endothelial and vascular smooth muscle cells, experiments were designed to determine whether a similar mechanism exists in IMCD cells. Cultured IMCD-3 cells derived from murine IMCD were subjected to 60 min of pulsatile shear stress. Nitrite production (2,3-diaminonaphthalene fluorometric assay) increased 12-, 16-, and 23-fold at 3.3, 10, and 30 dyn/cm(2), respectively, compared with static control cultures. Preincubation with the non-isoform-specific NO synthase inhibitor nitro-L-arginine methyl ester reduced nitrite production by 83% in response to 30 dyn/cm(2). Western blotting and immunofluorescence analysis of static IMCD-3 cell cultures revealed the expression of all three NO synthase isoforms (NOS-1 or neuronal NOS, NOS-2 or inducible NOS, and NOS-3 or endothelial NOS) in IMCD-3 cultures. These results indicate that NO production is modulated by shear stress in IMCD-3 cells and that fluid shear stress within the renal tubular system may play a role in the regulation of sodium and water excretion by control of NO production in the IMCD.
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PMID:Shear stress-mediated NO production in inner medullary collecting duct cells. 1091 45

Endothelin-1 (ET-1) inhibition of vasopressin (AVP)-stimulated cAMP accumulation in the collecting duct has been hypothesized to be mediated, at least in part, by nitric oxide (NO). To examine this, the effect of ET-1 on NO production by acutely isolated rat inner medullary collecting duct (IMCD) cell suspensions and the role of NO in mediating ET-1 effects on AVP-stimulated cAMP accumulation were studied. ET-1 dose dependently (first evident at 100 pM ET-1) increased IMCD NO production as determined by DAF-FM fluorescence. ET(B) receptor (BQ-788), but not ET(A) receptor (BQ-123), antagonism blocked this effect. Nonspecific NO synthase (NOS) inhibitors [N(G)-nitro-L-arginine methyl ester (L-NAME) or N(G)-monomethyl-L-arginine] or NOS-1 inhibitors (SMTC or VNIO) inhibited the ET-1 response, whereas NOS-2 or NOS-3 inhibitors (L-NAA or 1400W) were ineffective. ET-1 also increased cGMP accumulation. ET-1 caused a 35% reduction in AVP-stimulated cAMP levels; however, this response was not affected by L-NAME or SMTC. The addition of L-arginine, NADPH, tetrahydrobiopterin, or tempol (to reduce superoxide-dependent conversion of NO to peroxynitrate) did not affect the response. NO donors (SNAP or spermine NONOate), at concentrations that stimulated DAF-FM fluorescence and increased cGMP levels, did not alter AVP-stimulated cAMP accumulation in the IMCD cell suspensions. In conclusion, ET-1 stimulates IMCD NO production through activation of the ET(B) receptor and NOS-1. However, neither ET-1-mediated NO production nor NO donors inhibit AVP-stimulated cAMP accumulation, indicating that NO does not mediate ET-1 inhibition of cAMP production by the IMCD.
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PMID:Endothelin-1 stimulates NO production and inhibits cAMP accumulation in rat inner medullary collecting duct through independent pathways. 1638 Apr 57