Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:1.5.1.19 (NOS)
7,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renal microvascular actions of ACh were investigated using the in vitro perfused hydronephrotic rat kidney. ACh reversed ANG II-induced vasoconstriction in the afferent and efferent arteriole by 106 +/- 2 and 75 +/- 5%, respectively. Inhibition of nitric oxide synthase [NOS; 100 micromol/l N(G)-nitro-L-arginine methyl ester (L-NAME)] and cyclooxygenase (COX; 10 micromol/l ibuprofen) prevented the sustained response of the afferent arteriole but did not reduce the magnitude of the initial dilation (97 +/- 7%). However, NOS/COX inhibition abolished the response of the efferent arteriole. The underlying mechanisms mediating this endothelium-derived hyperpolarizing factor (EDHF)-like response were characterized using K channel blockers. Ba (100 micromol/l), tetraethylammonium (1 mmol/l), and ouabain (3 mmol/l) had no effect, arguing against a role of an inward rectifier K channel, large-conductance Ca-activated K channel, or Na,K-ATPase. Charybdotoxin (10 nmol/l) and apamin (1.0micromol/l) attenuated the response when administered alone (63 +/- 7% and 37 +/- 5%, respectively) and abolished the response when coadministered (0.1 +/- 1.0%). These findings indicate that, as in other vascular beds, the renal EDHF-like response to ACh involves K channels that are sensitive to a combination of apamin and charybdotoxin. Our finding that EDHF modulates preglomerular, but not postglomerular, tone is consistent with the evolving concept that vasomotor mechanisms in cortical efferent arterioles do not involve voltage-gated Ca entry.
...
PMID:Determinants of renal microvascular response to ACh: afferent and efferent arteriolar actions of EDHF. 1173 20

We evaluated the anti-inflammatory and neuroprotective effect of nonselective NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), in experimental bacterial meningitis in the newborn piglet. Meningitis was induced by intracisternal injection of 10(8) colony forming units of Escherichia coli. L-NAME 10 mg kg(-1) was given intravenously 30 min before induction of meningitis. L-NAME significantly attenuated the increase in intracranial pressure and decrease in cerebrospinal fluid glucose concentration observed in the meningitis group. Systemic and cerebral perfusion pressure were even higher compared to the control and meningitis groups. However, the meningitis-induced increase in tumor necrosis factor-alpha level, leukocyte numbers and lactate level in the cerebrospinal fluid was not significantly attenuated with L-NAME administration. Reduced cerebral cortical cell membrane Na+, K+ -ATPase activity and increased lipid peroxidation products, indicative of meningitis-induced brain cell membrane dysfunction, were significantly improved with L-NAME treatment. Decreased brain glucose and ATP levels were also significantly improved with L-NAME treatment. These findings suggest that L-NAME was effective in attenuating the acute inflammatory responses and brain injury in neonatal bacterial meningitis.
...
PMID:N(omega) -nitro-L-arginine methyl ester (L-NAME) attenuates the acute inflammatory responses and brain injury during the early phase of experimental Escherichia coli meningitis in the newborn piglet. 1176 Aug 79

1. The aim of the study was to investigate the mechanism of a novel effect of hypoxia on intracellular Ca(2+) signalling in rabbit cerebral arteriolar smooth muscle cells, an effect that was resistant to the L-type Ca(2+) channel antagonist methoxyverapamil (D600). 2.[Ca(2+)](i) of smooth muscle cells in intact arteriolar fragments was measured using the Ca(2+)-indicator dye fura-PE3. Hypoxia (PO(2) 10 - 20 mmHg) lowered basal [Ca(2+)](i) but did not inhibit Ca(2+) entry pathways measured by Mn(2+)-quenching of fura-PE3. 3. The effect of hypoxia was completely prevented by thapsigargin or cyclopiazonic acid, selective inhibitors of sarcoplasmic reticulum Ca(2+) ATPase (SERCA). Since these inhibitors do not block Ca(2+) extrusion or uptake via the plasma membrane, the data indicate that the effect of hypoxia depends on a functional sarcoplasmic reticulum. 4. Because actions of nitric oxide (NO) on vascular smooth muscle are also prevented by SERCA inhibitors it was explored whether the effect of hypoxia occurred via modulation of endogenous NO release. Residual NOS-I and NOS-III were detected by immunostaining, and there were NO-dependent effects of NOS inhibitors on Ca(2+)(i)-signalling. Nevertheless, inhibition of endogenous NO production did not prevent the effect of hypoxia on [Ca(2+)](i). 5. The experiments reveal a novel nitric oxide-independent effect of hypoxia that is prevented by SERCA inhibitors.
...
PMID:Prevention of a hypoxic Ca(2+)(i) response by SERCA inhibitors in cerebral arterioles. 1186 20

Nitric oxide (NO*) is produced endogenously from NOS isoforms bound to sarcolemmal (SL) and sarcoplasmic reticulum (SR) membranes. To investigate whether locally generated NO* directly affects the activity of enzymes mediating ion active transport, we studied whether knockout of selected NOS isoforms would affect the functions of cardiac SL (Na+ + K+)-ATPase and SR Ca2+-ATPase. Cardiac SL and SR vesicles containing either SL (Na+ + K+)-ATPase or SR Ca2+-ATPase were isolated from mice lacking either nNOS or eNOS, or both, and tested for enzyme activities. Western blot analysis revealed that absence of single or double NOS isoforms did not interrupt the protein expression of SL (Na+ + K+)-ATPase and SR Ca2+-ATPase in cardiac muscle cells. However, lack of NOS isoforms in cardiac muscle significantly altered both (Na+ + K+)-ATPase activity and SR Ca2+-ATPase function. Our experimental results suggest that disrupted endogenous NO* production may change local redox conditions and lead to an unbalanced free radical homeostasis in cardiac muscle cells which, in turn, may affect key enzyme activities and membrane ion active transport systems in the heart.
...
PMID:Lack of nitric oxide synthase depresses ion transporting enzyme function in cardiac muscle. 1207 80

We examined whether Ca(2+) mobilizers induce endothelium-dependent contraction and relaxation (EDC and EDR) in isolated rabbit intrapulmonary arteries. Ionomycin (10(-7) M) and A-23187 (10(-7) M), both Ca(2+) ionophores, and thapsigargin (10(-6) M), an endoplasmic reticulum Ca(2+)-ATPase inhibitor, caused a contraction in the non-contracted preparations, and a transient relaxation followed by a transient contraction and sustained relaxation in the precontracted preparations. Endothelium-removal abolished the contraction and transient relaxation (EDC and EDR) but not sustained relaxation (endothelium-independent relaxation, EIR). In the noncontracted preparations, ionomycin-induced EDC was significantly attenuated by quinacrine (10(-5) M), manoalide (10(-6) M), both phospholipase A(2) inhibitors, indomethacin (10(-5) M) and aspirin (10(-4) M), both COX inhibitors, and ozagrel (10(-5) M), a TXA(2) synthetase inhibitor. In the precontracted arteries, EDR was markedly reduced by L-NAME (10(-4) M), a NOS inhibitor, and methylene blue (10(-6) M), a guanylate cyclase inhibitor, and was enhanced by indomethacin, aspirin and ozagrel, probably due to inhibition of EDC. ZM230487, a 5-lipoxygenase inhibitor, had no effect on EDR. EIR was not affected by L-NAME, indomethacin or ZM230487. Arachidonic acid (10(-6) M) evoked EDC sensitive to indomethacin and ozagrel. L-Arginine (10(-3) M) caused EDR sensitive to L-NAME in the ionomycin-stimulated preparations. In conclusion, Ca(2+) mobilizers cause EDC and EDR via production of TXA(2) and NO, respectively.
...
PMID:Role of intracellular Ca2+ in endothelium-dependent contraction and relaxation of rabbit intrapulmonary arteries. 1258 21

Statins, 3-hydroxy-3-methylglutaryl CoA reductase inhibitors, acutely increase endothelial nitric oxide synthase (eNOS) activity and chronically increase eNOS expression in endothelial cells. NO decreases transport in thick ascending limbs (TAL). We hypothesized that statins inhibit TAL transport by acutely activating eNOS, thereby increasing NO production and chronically enhancing eNOS expression. Oxygen consumption (QO(2)) by TAL suspensions from Sprague-Dawley rats was used as a measure of active NaCl reabsorption. Na/K ATPase activity was assessed by measuring ATP hydrolysis in the presence and absence of ouabain. eNOS expression was measured by Western blot. A total of 50 micro M pravastatin decreased QO(2) by 18.6 +/- 3.4% (P < 0.01). In the presence of 500 micro M furosemide and 200 micro M amiloride, transport blockers, QO(2) remained the same after pravastatin was added. Na/K ATPase activity was not different from controls and TAL treated with 50 micro M pravastatin (0.33 +/- 0.07 versus 0.29 +/- 0.04 nmol P(i)/ micro g protein/min, where P(i) is inorganic phosphate). Nystatin stimulated QO(2) to 178 +/- 13.7 in pravastatin-treated TAL and 195 +/- 11.5 in furosemide-treated TAL. The inhibitory effect of pravastatin on QO(2) was blocked by L-nitroarginine methyl ester, an NOS inhibitor. In addition, pravastatin increased NO production as measured by the fluorescent dye DAF-2A. Pravastatin at a dose of 10 mg/kg per d had no effect on eNOS protein at 1 d (24.1 +/- 2.7 versus 25.5 +/- 1.1 arbitrary units [AU]) or 7 d (24.1 +/- 2.7 versus 20.9 +/- 1.3 AU). Similarly, at 1 d, 50 mg/kg per d had no effect on expression (24.1 +/- 2.7 versus 21.2 +/- 3.6 AU). At 7 d, this dose decreased eNOS protein from 24.1 +/- 2.7 to 11.8 +/- 4.4 AU. It is concluded that pravastatin acutely decreases NaCl entry into the TAL by releasing NO. Pravastatin does not chronically increase eNOS expression in TAL.
...
PMID:Acute and chronic regulation of thick ascending limb endothelial nitric oxide synthase by statins. 1474 73

Excessive excitatory action of glutamate and nitric oxide (NO) has been implicated in degeneration of striatal neurons. Evidence had been provided that Na+K+-ATPase might be involved in this process. Here we investigated whether glutamate-regulated messengers, such as NO and cyclic GMP, could modulate the activity of membrane Na+K+-ATPase. Our results demonstrated that NO donors sodium nitroprusside (SNP at 30 and 300 microM) and S-nitroso-N-acetylpenicillamine (SNAP at 200 microM) increased alpha2,3Na+K+-ATPase activity which was blocked by the NO chelator, haemoglobin and was independent of [Na+]. This regulation was associated with cGMP synthesis and mimicked by glutamate (300 microM) and 8-Br-cyclic GMP (4 mM). 8-Br-cGMP-induced stimulation of Na+K+-ATPase activity could be blocked by KT5823 (an inhibitor of cGMP-dependent protein kinase, PKG), but not by KT5720 (an inhibitor of cAMP-dependent protein kinase, PKA). N-Methyl-D-aspartate (NMDA) receptors appeared to be involved in the effect of glutamate, since MK-801 (NMDA receptor antagonist) produced a partial reduction in glutamate-induced activation of the enzyme. MK-801 was not synergistic to L-NAME (NOS inhibitor), suggesting that glutamate stimulates the NMDA-NOS pathway to activate alpha2,3 Na+K+-ATPase in rat striatum. This regulation was associated with cyclic GMP (but not cyclic AMP) synthesis. These data indicate the existence, in vitro, of a regulatory pathway by which glutamate, acting through NO and cGMP, can cause alterations in striatal alpha2,3 Na+K+-ATPase activity.
...
PMID:Glutamate modulates sodium-potassium-ATPase through cyclic GMP and cyclic GMP-dependent protein kinase in rat striatum. 1562 18

Na+K+-ATPase is an important enzyme serving vital functions in various mammalian tissues, including the intestine. We have previously documented that endotoxin (LPS) and nitric oxide (NO) can induce enterocyte injury in vitro. To examine whether alterations Na+,K+-ATPase activity might be involved in LPS- or NO-induced enterocyte dysfunction, we carried out four series of experiments. The first set of experiments documented that LPS decreases IEC-6 Na+,K+-ATPase activity at concentrations as low as 0.10 microg/ml. The second set of experiments tested whether exposure of IEC-6 cells to the exogenous NO donor, S-Nitroso-N-acetylpenicillamine (SNAP), would decrease IEC-6 Na+,K+-ATPase activity. The results of these experiments documented that SNAP significantly decreased IEC-6 Na+,K+-ATPase activity in a dose-dependent fashion at a threshold inhibitory concentration of 0.1 mM, and there was an inverse correlation between Na+,K+-ATPase activity and NO concentrations in the medium. Since enterocytes contain iNOS, and LPS can increase iNOS activity, the third set of experiments examined the relationship between LPS-induced inhibition of Na+),K+-ATPase activity and NO production by the IEC-6 cells. These results showed that LPS increased IEC-6 NO production in both a dose- and time-dependent fashion and an inverse correlation existed between LPS-induced NO production and decreased Na+,K+-ATPase activity. Addition of the NOS inhibitor, L-NNA, prevented the LPS-induced decrease in Na+,K+ATPase activity, suggesting that NO is involved in the decrease of Na+,K+-ATPase activity observed in the IEC-6 cells incubated with LPS. One mechanism by which the increased NO concentrations could have contributed to the decrease in Na+,K+ATPase activity, after the addition of LPS or SNAP, is via the production of peroxynitrite during the reaction of NO with superoxide. This notion was supported by studies showing that SNAP- and LPS-induced decreases in IEC-6 Na+,K+-ATPase activity could be blocked by adding superoxide dismutase to the medium. The last set of experiments tested whether the inhibition of Na+,K+-ATPase activity with the specific Na+,K+-ATPase inhibitor ouabain would increase the permeability of an IEC-6 monolayer. IEC-6 monolayer permeability was increased by ouabain, but only at a high concentration. In conclusion, these studies indicate that LPS or the NO donor, SNAP, inhibit Na+,K+-ATPase activity and this inhibition is at least partly related to peroxynitrite production. These studies also suggest that LPS-induced NO production by the IEC-6 cells decreases IEC-6 Na+,K+-ATPase activity in an autocrine fashion.
...
PMID:Na+,K+-ATPase activity is inhibited in cultured intestinal epithelial cells by endotoxin or nitric oxide. 1580 12

The proinflammatory cytokine interleukin-1 (IL-1) promotes the degradation of articular cartilage by inhibiting matrix synthesis and stimulating degradative enzyme activity. Generation of nitric oxide (NO) in response to IL-1 is implicated in these actions. The catabolic actions of IL-1 can be inhibited by manoeuvres which are predicted to dissipate H+ gradients across the chondrocyte plasma membrane. In the present study, the effects of IL-1 on H+ extrusion from bovine articular chondrocytes were investigated. pH was measured using the H+-sensitive fluorescent dye BCECF. Cells were acidified by ammonium rebound and the contribution of the Na+-H+ exchanger (NHE) and of the vacuolar H+-ATPase to acid extrusion was characterised by ion substitution and inhibitor studies. Overnight (18 h) exposure to IL-1 stimulated acid extrusion in a dose-dependent fashion. This effect represented stimulation of both NHE and the ATPase. Characterisation of the timecourse of this response indicated that, while stimulation of acid extrusion was rapid, effects on the ATPase were only apparent after greater than 8h incubation with the cytokine. In keeping with this observation, the protein synthesis inhibitor cycloheximide abolished the stimulatory effect of IL-1 on ATPase-mediated extrusion. The upregulation of ATPase activity by IL-1 was inhibited by the NOS inhibitor L-NAME and by the NO scavenger PTIO. In cells which had not been exposed to IL-1, treatment with the NO donor SNAP also stimulated acid extrusion by the ATPase. In contrast, NHE activity was not altered by any of these compounds. Taken together, these results imply that IL-1 can stimulate acid extrusion in chondrocytes and that this reflects rapid upregulation of NHE with slower induction of H+-ATPase activity which requires elevated levels of NO. While ATPase induction involves protein synthesis, this process may not constitute synthesis of ATPase proteins per se, but rather of some associated regulatory process.
...
PMID:Modulation of H+ transport mechanisms by interleukin-1 in isolated bovine articular chondrocytes. 1612 Oct 32

Passage of spermatozoa through the epididymis is obligatory for sperm maturation processes and is based on spontaneous phasic contractions (SC) of the epididymal duct. Here, the functional role of cyclic GMP (cGMP) signaling in modulating SC in the bovine epididymal caput and corpus region was examined by muscle tension recording and immunological and autoradiographic techniques. The cGMP-analog 8-bromo (Br)-cGMP, as well as the nitric oxide (NO) donor sodium nitroprusside and the natriuretic peptides (NPs) atrial NP and C-type NP, displayed distally increasing SC-relaxant effects. In agreement, a distally increasing epididymal expression of the cGMP-dependent protein kinase I (PKG I), endothelial NO synthase (eNOS), and the atrial NP receptor was found. Immunoreactivity for PKG, soluble guanylate cyclase, and eNOS could be localized to the epididymal muscle cells as well as to the epithelial basal cells only at the corpus level. The SC-relevant action of NO and the NPs was cGMP dependent, and the action of 8-Br-cGMP, in turn, was modified by epithelial and luminal factors. The NOS inhibitor L-NAME (N(omega)-nitro-L-arginine methyl ester) caused an increase in SC frequency, indicating basal activity of NO generating enzymes. The SC-inhibitory effect of 8-Br-cGMP was clearly reduced by the PKG inhibitor Rp-8-Br-cGMPS as well as by iberiotoxin, thapsigargin, and indomethacin, pointing to PKG as main SC-relevant target of cGMP, and to large-conductance calcium-activated K(+) channels, the sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase and cyclooxygenase-1 as possible targets of PKG. These data support an essential role of cGMP signaling in the control of epididymal peristalsis, thereby enabling fine tuning of sperm transport and maturation.
...
PMID:Regulation of spontaneous contractile activity in the bovine epididymal duct by cyclic guanosine 5'-monophosphate-dependent pathways. 1643 52


<< Previous 1 2 3 4 5 6 Next >>

---