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)

Stimulation of the release of nitric oxide (NO) in the kidney has been shown to result in renal hemodynamic changes and natriuresis. NO is a potent stimulator of soluble guanylate cyclase, leading to an increase of cyclic GMP. The precise localization of NO synthase and soluble guanylate cyclase in the renal structure is not known. In this study, the microlocalization of mRNAs coding for constitutive NO synthase and soluble guanylate cyclase was carried out in the rat kidney, using an assay of reverse transcription and polymerase chain reaction in individual microdissected renal tubule segments along the nephron, glomeruli, vasa recta bundle, and arcuate arteries. A large signal for constitutive NO synthase was detected in inner medullary collecting duct. Small signals were detected in inner medullary thin limb, cortical collecting duct, outer medullary collecting duct, glomerulus, vasa recta, and arcuate artery. Soluble guanylate cyclase mRNA is expressed largely in glomerulus, proximal convoluted tubule, proximal straight tubule, and cortical collecting duct, and in small amounts in medullary thick ascending limb, inner medullary thin limb, outer medullary collecting duct, inner medullary collecting duct, and the vascular system. Our data demonstrate that NO can be produced locally in the kidney, and that soluble guanylate cyclase is widely distributed in glomerulus, renal tubules, and the vascular system.
 ...
PMID:Polymerase chain reaction localization of constitutive nitric oxide synthase and soluble guanylate cyclase messenger RNAs in microdissected rat nephron segments. 137 16

The characterization and cloning of constitutive and inducible nitric oxide (NO)-synthesizing enzymes and the development of specific inhibitors of the L-arginine NO pathway have provided powerful tools to define the role of NO in renal physiology and pathophysiology. There is increasing evidence that endothelium-derived NO is tonically synthesized within the kidney and that NO plays a crucial role in the regulation of renal hemodynamics and excretory function. Bradykinin and acetylcholine induce renal vasodilation by increasing NO synthesis, which in turn leads to enhancement of diuresis and natriuresis. The blockade of basal NO synthesis has been shown to result in decreases of renal blood flow and sodium excretion. These effects are partly mediated by an interaction between NO and the renin angiotensin system. Intrarenal inhibition of NO synthesis leads to reduction of sodium excretory responses to changes in renal arterial pressure without an effect on renal autoregulation, suggesting that NO exerts a permissive or a mediatory role in pressure natriuresis. Nitric oxide released from the macula densa may modulate tubuloglomerular feedback response by affecting afferent arteriolar constriction. Nitric oxide produced in the proximal tubule possibly mediates the effects of angiotensin on tubular reabsorption. In the collecting duct, an NO-dependent inhibition of solute transport is suggested. The L-arginine NO pathway is also active in the glomerulus. Under pathologic conditions such as glomerulonephritis, NO generation is markedly enhanced due to the induction of NO synthase, which is mainly derived from infiltrating macrophages. An implication of NO in the mechanism of proteinuria, thrombosis mesangial proliferation, and leukocyte infiltration is considered. In summary, the data presented on NO and renal function have an obvious clinical implication. A role for NO in glomerular pathology has been established. Nitric oxide is the only vasodilator that closely corresponds to the characteristics of essential hypertension. Using chronic NO blockade, models of systemic hypertension will provide new insights into mechanisms of the development of high blood pressure.
 ...
PMID:Nitric oxide in the kidney: synthesis, localization, and function. 751 25

Nitric oxide (NO) is a messenger molecule that is produced from L-arginine by NO synthase (NOS). Some NOS isoforms are present in cells constitutively, whereas others can be induced by cytokines. Recent evidence suggests that NO inhibits intracellular pH regulation by the vacuolar H(+)-adenosinetriphosphatase (ATPase) in macrophages, which contain an inducible form of NOS. The vacuolar H(+)-ATPase is involved in proton secretion in intercalated cells in the collecting duct. We have therefore examined the effect of NO on bafilomycin-sensitive H(+)-ATPase activity in individual cortical collecting ducts (CCD) microdissected from collagenase-treated kidneys of normal rats using a fluorometric microassay. Incubation of CCD with the NO donors, sodium nitroprusside (0.1 and 1 mM) or 3-morpholino-sydnonimine hydrochloride (SIN-1, 30 microM), caused a dose-dependent decrease in H(+)-ATPase activity. Incubation of CCD with lipopolysaccharide (LPS) and interferon-gamma, which induces NOS in macrophages, decreased H(+)-ATPase activity by 85%. This effect was prevented by simultaneous incubation with N omega-nitro-L-arginine, a competitive inhibitor of NOS, indicating that the decrease in H(+)-ATPase activity was caused by NO production. Incubation with 8-bromo-guanosine 3',5'-cyclic monophosphate (cGMP) also inhibited H(+)-ATPase activity, suggesting that NO may exert its effect in the CCD via activation of guanylyl cyclase and production of cGMP. Immunohistochemistry using antibodies to the macrophage-type NOS revealed strong labeling of intercalated cells in the CCD, confirming the presence of NOS in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Nitric oxide inhibits bafilomycin-sensitive H(+)-ATPase activity in rat cortical collecting duct. 752 55

Endothelins (ET) possess both vasodilatory and vasoconstrictive properties. The renal actions of ET-1 and ET-3, as well as in vivo interactions of these two isopeptides with the prostaglandin and endothelium-derived relaxation factor/nitric oxide systems were studied in anesthetized dogs. The ETs were infused intrarenally at doses not affecting systemic hemodynamics. Both ET-1 and ET-3 induced an early transient renal vasodilation, followed by a prolonged vasoconstriction. Inhibition of nitric oxide synthase with NG-monomethyl-L-arginine completely abolished the renal vasodilation induced by either ET-1 or ET-3 and enhanced the vasoconstriction. Endothelin-1 was associated with an increase in the renal release of prostacyclin, while urinary thromboxane A2 was increased after ET-3 administration. Inhibition of cyclooxygenase (with indomethacin) augmented the renal vasoconstriction induced by ET-1, but inhibition of cyclooxygenase (with meclofenamate) abolished the ET-3-evoked vasoconstriction. Endothelin-1 showed little effects on urinary water and sodium excretion; however, ET-3 displayed significant diuretic and natriuretic effects, which were inhibited by nitric oxide synthase inhibition. These findings suggest that these two isopeptides activate the endothelial endothelium-derived relaxation factor/nitric oxide system, which elicits early renal vasodilation, whereas direct effects on the vascular smooth muscle leads to vasoconstriction. Endothelin-3 causes diuresis and natriuresis, possibly by inducing release of nitric oxide in medullary collecting duct cells.
 ...
PMID:Renal actions of endothelin-1 and endothelin-3: interactions with the prostaglandin system and nitric oxide. 754 37

Nitric oxide (NO.) has been implicated in the regulation of renal vascular tone and tubular sodium transport. While the endothelial cell is a well known source of NO(.), recent studies suggest that tubular epithelial cells may constitutively generate NO(.). An inducible isoform of nitric oxide synthase which produces far greater quantities of NO. exists in some cell types. We sought to determine whether kidney epithelial cells exposed to cytokines could express an inducible nitric oxide synthase. Primary cultures of rat proximal tubule and inner medullary collecting duct cells generated NO. on exposure to TNF-alpha and IFN-gamma. NO. production by both cell types was inhibited by NG-monomethyl-L-arginine; this inhibition was partially reversed by the addition of excess L-arginine. Stimulation of kidney epithelial cells with TNF-alpha and IFN-gamma dramatically increased the level of inducible nitric oxide synthase mRNA. In summary, renal proximal tubule and inner medullary collecting duct cells can produce NO. via expression of an inducible isoform of nitric oxide synthase.
 ...
PMID:Cytokine-induced expression of a nitric oxide synthase in rat renal tubule cells. 768 98

Stimulation of soluble guanylyl cyclase (SGC) by nitric oxide (NO) results in the generation of cyclic guanosine monophosphate (cGMP). We recently described expression of abundant nitric oxide synthase, the enzyme by which NO is generated from L-arginine in macula densa cells of rat kidney at the protein and mRNA level. In the present study we looked for possible targets of NO in the kidney. By light and electron microscopy, we applied polyclonal antisera against four subunits (alpha 1, alpha 2, beta 1, beta 2) of SGC in immunocytochemical studies of frozen sections of rat kidney. We demonstrate the presence of alpha 1-subunit in glomerular podocytes and of beta 2-subunit in principal cells of the collecting duct. In both cell types a cytosolic localization was evident from ultrastructural analysis. Regarding the collecting duct, NO was shown by other authors to inhibit sodium reabsorption in cultured mouse cortical collecting duct principal cells. In podocytes NO may relax the contractile system of podocyte food processes, the tone of which has been suggested to counteract the elastic distension of the capillary wall.
 ...
PMID:Immunolocalization of soluble guanylyl cyclase subunits in rat kidney. 773 83

Two types of K+ channels, low conductance (28 pS) and intermediate conductance (85 pS), have been previously identified in the basolateral membrane of the cortical collecting duct (CCD) of the rat kidney (31, 32). In the present study, we used the patch-clamp technique to explore further the mechanism by which the low-conductance K+ channel is regulated. The conductance of the low-conductance K+ channel is inward rectifying, with an inward slope conductance of 30 pS between 0 and -20 mV and an outward slope conductance of 16 pS between 0 and 50 mV in symmetrical 140 mM KCl in the bath and in the pipette. This K+ channel was not sensitive to ATP (10 mM), tetraethylammonium chloride (5 mM), and quinidine (1 mM). Addition of 100 microM N omega-nitro-L-arginine methyl ester (L-NAME) or N omega-(imonoethyl)-L-ornithine (L-NIO), an inhibitor of nitric oxide synthase (NOS), completely blocked channel activity in cell-attached patches. In contrast, addition of 200 microM-D-NAME, which does not block NOS, had no effect on channel activity. The inhibitory effect of L-NAME or L-NIO was fully reversible and completely overcome by addition of exogenous nitric oxide (NO) donors, such as 10 microM S-nitroso-N-acetyl-penicillamine or sodium nitroprusside. Furthermore, addition of 100 microM 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) restored the activity of the channel when it had been inhibited by either L-NAME or L-NIO, indicating that the effect of NO on the channel activity was mediated by a cGMP-dependent pathway. In conclusion, NO plays a key role in the regulation of the basolateral 30-pS K+ channel and the effect of NO on channel activity is mediated by a cGMP-dependent pathway.
 ...
PMID:Nitric oxide regulates the low-conductance K+ channel in basolateral membrane of cortical collecting duct. 896 33

Nitric oxide synthase has been identified in several epithelial cells in the kidney, including proximal tubular cells, thick ascending limb, inner medullary collecting duct, and interstitial cells. Nitric oxide (NO) plays an important role in renal hemodynamics and sodium tubular transport. We have demonstrated that NO participates in hypoxia/reoxygenation (H/R) injury in isolated rat proximal tubules (PT) suspensions. In this in vitro model L-arginine addition enhanced H/R injury while L-NAME almost completely prevented injury. These effects were less intense in chronic supplemented rats with L-arginine and L-NAME, suggesting that NO synthase manipulation had interfered with PT susceptibility to H/R injury. In contrast, L-arginine protected IMCD cells in culture from hypercholesterolemic rats against hypoxia. Moreover, acute infusion of L-arginine before bilateral renal artery clamping was protective while L-arginine chronic administration and L-NAME were deleterious in this ARF model. The L-arginine protection was not observed in unilateral renal clamping plus contralateral nephrectomy in normal rats, but L-arginine was protective in hypercholesterolemic rats. Taken together, these results suggest that the net effect of NO stimulation is variable, and that it is the result of a balance between beneficial hemodynamic effects and cytotoxicity.
 ...
PMID:Role of nitric oxide in acute renal failure. 910 93

We used the patch-clamp technique in the split-open cortical collecting duct (CCD) to investigate the effect of nitric oxide (NO) on the low-conductance (6-pS) Na+ channel that can be blocked by 1 microM amiloride. We confirmed that the number of Na+ channels increased significantly in CCDs of rats on a low-Na+ diet (17). Application of 100 microM N(G)-nitro-L-arginine methyl ester (L-NAME), an agent that blocks endogenous NO synthase, reduced NPo [the product of channel number (N) and open probability (Po)] to 45% of the control value. The effect of L-NAME was specific, since addition of D-NAME, which does not inhibit NO synthase, did not change the activity of the Na+ channel. That the effect of L-NAME results from inhibition of NO synthase is further confirmed by experiments in which addition of an exogenous NO donor, either 10 microM S-nitroso-N-acetyl penicillamine or sodium nitroprusside (SNP), restored the Na+ channel activity when it had been blocked by L-NAME. The action of NO involves a guanosine 3',5'-cyclic monophosphate (cGMP)-dependent pathway, since 100 microM 8-bromo-cGMP (8-BrcGMP) mimicked the effect of SNAP on K+ channels. However, 100 microM 8-BrcGMP did not alter the activity of Na+ channels in inside-out patches, suggesting an indirect action. Because the Na+ channel is activated by hyperpolarization (19) and NO stimulates basolateral K+ channels (16), we tested whether hyperpolarization mediated the effect of NO. In perforated whole cell recordings, addition of L-NAME depolarized the cell membrane from -73 to 51 mV, and application of 10 microM SNP repolarized the membrane to -68 mV. Furthermore, the L-NAME-induced decrease in NPo was effectively restored by 25 mV hyperpolarization of the patch membranes, and addition of 2 mM Ba2+ also abolished the effect of L-NAME. We concluded that the stimulatory effect of NO on the Na+ channel is an indirect effect mediated by a NO-induced increase of basolateral K+ conductance.
 ...
PMID:Nitric oxide-induced hyperpolarization stimulates low-conductance Na+ channel of rat CCD. 914 51

1. Recent studies have indicated that nitric oxide (NO) production in the kidney contributes to the regulation of renal haemodynamics and excretory function. Inhibition of nitric oxide synthase (NOS) reduces renal blood flow by approximately 25% and markedly reduces sodium excretion without reductions in filtered load. In particular, inhibition of NO synthesis markedly suppresses the slope of the arterial pressure-mediated response in sodium excretion. 2. Further studies have shown that constant intrarenal infusion of a NO donor in dogs treated with a NOS inhibitor produced diuretic and natriuretic responses but failed to restore the slope of the pressure-induced natriuretic response. These data indicate that an alteration in intrarenal NO activity, rather than the simple presence of NO during changes in arterial pressure is required for full expression of pressure natriuretic responses. 3. In support of the hypothesis that NO is involved in the mediation of pressure natriuresis, we also recently demonstrated a direct relationship between changes in arterial pressure and urinary excretion rate of sodium as well as nitrate and nitrite (a marker for endogenous NO activity) in the presence of efficient autoregulation of cortical and medullary blood flow. 4. The direct inhibitory actions of NO on tubular sodium reabsorption have also been observed in cultured tubular cells as well as isolated, perfused cortical collecting duct segments. 5. Thus, the collective data suggest that acute changes in arterial pressure induce changes in intrarenal NO production, which may directly alter tubular reabsorptive function to manifest the phenomenon of pressure natriuresis.
 ...
PMID:Nitric oxide in the mediation of pressure natriuresis. 926 34


1 2 3 4 5 6 Next >>