Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A study has been made of the modulation of high-voltage activated transient and sustained calcium currents in cultured neurones of avian ciliary ganglia by nitric oxide (NO) and arachidonic acid. 2. Sodium nitroprusside (100 microM) reduced the transient calcium current (ICa) on average by 31% and the sustained ICa by 32% during a test depolarization to +20 mV from a holding potential of -100 mV. This reduction was maintained for at least 30 min following a single application of sodium nitroprusside. 3. L-Arginine (270 microM) reduced the transient ICa on average by 28% and the sustained ICa by 22% and these effects were prevented by the presence of the NO-synthase competitive blocker NG-nitro-L-arginine methylester (L-NAME; 100 microM) in the bathing solution. 4. Arachidonic acid (50 microM) reduced the transient ICa on average by 28% and the sustained ICa by 33%. When added together, arachidonic acid (50 microM) and L-arginine (270 microM) produced the same effects as arachidonic acid alone. 5. Blocking the conversion of arachidonic acid to prostaglandins by addition of indomethacin (20 microM) to the bathing solution did not prevent the depression of either the transient or the sustained calcium current during application of arachidonic acid (50 microM). The effects of arachidonic acid were also not occluded by L-NAME (100 microM) when present in the bathing solution. 6. Inhibiting the biosynthesis of leukotrienes by applying L-663,536 (MK-886; 3 microM) to the bathing solution prevented the depression of both components of ICa during application of arachidonic acid (50 microM). 7. These results indicate that endogenous NO and arachidonic acid pathways are present in parasympathetic ciliary neurones, and that both act to depress high-voltage, gated, calcium channel activity.
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PMID:Nitric oxide and arachidonic acid modulation of calcium currents in postganglionic neurones of avian cultured ciliary ganglia. 839 90

In anesthetized, ventilated pigs we analyzed the involvement of nitric oxide (NO) and prostaglandins (PGs) in the regulation of systemic and pulmonary basal vascular tone. Endogenous release of NO was blocked by NG-nitro-L-arginine methyl ester (L-NAME) and prostanoid biosynthesis by indomethacin. Blocking NO raised pulmonary and systemic arterial pressure and vascular resistances. These effects show that in the pig there is continuous release of minute amounts of NO. Blocking prostanoid biosynthesis did not affect the vasoconstrictor effect of L-NAME on the pulmonary vascular bed, but significantly strengthened the hypertensive effect of L-NAME on the systemic vascular bed. These data show that different mechanisms regulate pulmonary and systemic vascular tone. Administration of a stable analogue of PGI2 to pigs pretreated with indomethacin reversed the systemic vasoconstrictor effect of L-NAME. In conclusion, our data show that NO especially modulates pulmonary vascular tone, while PGI2 preferentially modulates systemic vascular tone.
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PMID:PGI2 and nitric oxide involvement in the regulation of systemic and pulmonary basal vascular tone in the pig. 880 24

The effects of inhibition of nitric oxide (NO) or serotonin (injection of nitro-L-arginine methyl ester (L-NAME) or 5,6-dihydroxytryptamine (5,6-DHT), respectively) on food-attraction conditioning was investigated in Helix. Blocking NO synthase (NOS) prior to conditioning significantly impaired the food-finding ability of the snails. Food-conditioned snails, after inhibition of NOS, remained able to locate the conditioned food. These results indicate that the acquisition of memory depends on NO, whereas memory recall and olfactory orientation are not dependent. Ablating the serotonergic system did not influence food-attraction conditioning, suggesting that food-attraction conditioning may be at variance with conventional associative conditioning procedures.
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PMID:Nitric oxide, but not serotonin, is involved in acquisition of food-attraction conditioning in the snail Helix pomatia. 884 74

In the present study peripheral T cell tolerance and the occurrence of shock were evaluated in young and old mice after injection of Staphylococcal enterotoxin B (SEB). In young mice SEB immunization leads to tolerance based on deletion and anergy of SEB-reactive V beta 8+ T cells. With aging, mice developed resistance to SEB-induced deletion of V beta 8+ T cells as well as a high sensitivity to toxic shock. Compared to young mice, older mice injected with SEB showed increased serum levels of interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and IL-4. These results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR), as splenic mRNA levels taken 2 h after SEB injection showed higher values of IL-2, IL-4, and IFN-gamma in old mice. In contrast, mRNA levels for FasL and tumour necrosis factor-alpha (TNF-alpha) were lower. No difference in IL-10 mRNA was found. Compared to young mice, old mice showed a high, but statistically not significantly different (P = 0.20), production of nitric oxide (NO). Blocking of IFN-gamma with antibodies or reducing IFN-gamma by depletion of natural killer (NK) cells resulted, respectively, in a complete or partial protection against mortality in aged mice. Suppressing the NO production by the NO synthase inhibitor N-nitro-L-arginine methylester (L-NAME) increased the mortality in both young and old mice, and abrogated clonal deletion in the surviving young mice. In conclusion, in young mice NO production is a key factor in the protection against mortality and the development of clonal deletion after SEB injection. The higher mortality seen in older mice is mainly related to the elevated production of IFN-gamma and occurs despite a sufficient production of NO. The decreased clonal deletion of old mice may be related to their decreased expression of Fas ligand or TNF-alpha after SEB injection.
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PMID:Increased mortality and impaired clonal deletion after staphylococcal enterotoxin B injection in old mice: relation to cytokines and nitric oxide production. 939 29

Many types of cells in the immune system have been found to produce nitric oxide (NO), which performs multiplex functions. However, in myelin basic protein peptide 68-86 (MBP 68-86)-induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats, we found that elevated NO production was generated from spleen cells (SC), not from lymph node cells (LNC). LNC expressed lower NO synthase 2 (NOS2) and produced lower levels of NO than SC upon MBP 68-86 stimulation. Expression of B7-1(CD80) and B7-2(CD86) molecules was much lower on LNC than on SC. Blocking of B7-1 or B7-2 ligation resulted in reduced NO production by SC. Unlike SC, LNC were resistant to interferon-gamma- or lipopolysaccharide-induced NO production. NO derived from SC suppressed cell proliferation and induced apoptosis in vitro. Addition of N(omega)-nitrol-L-arginine methylester (L-NAME) into cell cultures promoted cell expansion and reduced apoptosis. These results indicate that NO production originates from SC, but not from LNC. Low expression of co-stimulatory molecules and NOS2 of LNC limits NO induction. The high levels of NO derived from SC are involved in the self-limiting mechanisms of autoimmune responses by inhibiting cell expansion and promoting cell apoptosis.
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PMID:Limitation of nitric oxide production: cells from lymph node and spleen exhibit distinct difference in nitric oxide production. 1072 70

Exposure to uncontrollable aversive events produces a variety of behavioral consequences that do not occur if the aversive event is controllable. Accumulating evidence suggests that exaggerated excitation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is sufficient to cause these same behaviors, such as poor shuttlebox escape performance and enhanced conditioned fear that occur 24 h after exposure to inescapable tailshock (IS). The aim of the present studies was to explore the possibility that N-methyl-D-aspartate (NMDA) receptor activation and nitric oxide (NO) formation within the DRN might be involved in mediating the behavioral consequences of IS. To this end, either the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV) or the nitric oxide synthase inhibitor Nw-nitro-L-arginine methyl ester (L-NAME), was microinjected into the DRN before IS or before testing 24 h later. Blocking NMDA receptors with APV in the DRN during IS prevented the usual impact of IS on escape responding and conditioned fear. However, injection of APV at the time of testing only reduced these effects. The DRN was shown to be the critical site mediating blockade of these behavioral changes since injection of APV lateral to the DRN did not alter the behavioral consequences of IS. Conversely, L-NAME was most effective in reversing the effects of IS when administered at the time of testing. These results suggest that there is glutamatergic input to the DRN at the time of IS that produces long-lasting changes in DRN sensitivity. This plasticity in the DRN is discussed as a possible mechanism by which IS leads to changes in escape performance and conditioned fear responding.
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PMID:Impaired escape performance and enhanced conditioned fear in rats following exposure to an uncontrollable stressor are mediated by glutamate and nitric oxide in the dorsal raphe nucleus. 1086 33

We tested the hypothesis that low-dose ethanol would reduce cardiac myocyte function through increased production in the nitric oxide/cyclic GMP signal transduction pathway, rather than reduced degradation. Ventricular myocytes were isolated from the hearts of 9 rabbits. Myocyte function was studied using a video-edge detector and cyclic GMP levels were measured by radioimmunoassay. Cells were administered 5 and 10 mmol/l ethanol alone or after 10(-6) mol/l N(G)-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor), 10(-6) mol/l 1H-[1,2,4]oxadiazolo[4,3a]quinoxalin-1-one (ODQ, soluble guanylyl cyclase inhibitor) or 10(-5) mol/l zaprinast (cyclic GMP phosphodiesterase inhibitor). Ethanol (10 mmol/l) significantly decreased percent shortening from 10.0 +/- 0.9 to 6.0 +/- 0.2%. Similar decrements occurred in the maximum rate of shortening and relaxation. After L-NAME or ODQ, the decrements in percent shortening, maximum rate of shortening and relaxation caused by ethanol were not significant. After zaprinast, ethanol significantly decreased the maximum rate of shortening and relaxation and percent shortening to 4.3 +/- 0.5. Ethanol (10 mmol/l) significantly increased cyclic GMP from 403 +/- 121 to 529 +/- 128 fmol/10(5) myocytes. Both L-NAME and ODQ lowered cyclic GMP, and ethanol did not affect cyclic GMP after either. Zaprinast raised cyclic GMP, as did its combination with 10 mmol/l ethanol (653 +/- 120). Thus, ethanol both reduced myocyte function and increased cyclic GMP. Blocking nitric oxide production or guanylyl cyclase activity prevent these effects of ethanol, while blocking cyclic GMP degradation did not. This suggests that ethanol acts as a nitric oxide stimulator in ventricular myocytes leading to reduced function and increased cyclic GMP.
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PMID:Ethanol reduces cardiac myocyte function through activation of the nitric oxide-cyclic GMP pathway. 1256 49

We compared the phenotype of two common mouse models, C-57BL/6J (C57), which carries only the Ren-1c gene, and 129/SvJ (Sv-129), with both Ren 1d and Ren-2. We hypothesized two renin gene Sv-129 would have increased blood pressure and the renin-angiotensin system would be more influential in regulating renal function compared with one renin gene mice. Sv-129 consistently had higher blood pressure than C-57, whether conscious (128 versus 108 mm Hg, P<0.001) or anesthetized (102 versus 88 mm Hg, P<0.001). Plasma renin concentration in both conscious and anesthetized C-57 mice was 3- to 4-fold higher than in Sv-129 (P<0.05), whereas renal cortical renin content was 2.5-fold higher (P<0.005). Renal blood flow and renal vascular resistance were the same in C-57 and Sv-129. Exogenous angiotensinogen produced identical pressor and renal vasoconstrictor responses in both strains. Blocking AT1 receptors with losartan reduced blood pressure by 19 mm Hg in both strains. Nitric oxide synthase inhibition by l-NAME increased blood pressure by 29 mm Hg in C-57 and 35 mm Hg in Sv-129 mice, but the decrease in renal blood flow was 30% less in C-57 (P<0.025). We conclude that Sv-129 mice with two renin genes have higher blood pressure but lower plasma and renal renin than C-57 mice with one renin gene. Renin substrate may limit angiotensin II production in the mouse. In Sv-129, the influence of nitric oxide on renal but not systemic resistance may be exaggerated. Renin from Ren-2 may act independently of normal renin control mechanisms.
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PMID:Cardiovascular and renal phenotype in mice with one or two renin genes. 1466 50

Osteoclasts, cells primarily responsible for bone resorption, differentiate from hematopoietic progenitor cells under the influence of various hormones, cytokines, and differentiation factors. Once fully differentiated, osteoclasts rapidly die in the absence of any survival factor. We have previously shown that tumor necrosis factor alpha (TNF-alpha) promotes the survival of differentiated osteoclasts. The expression of inducible nitric oxide synthase (iNOS) and consequent NO production is often stimulated under inflammatory conditions. In this study, we found that TNF-alpha, but not receptor activator of nuclear factor kappa B ligand and interleukin 1, increased the expression of iNOS both at the mRNA and protein levels. Subsequently, an enhanced NO level was detected both inside the cells and the culture medium of TNF-alpha-stimulated osteoclasts. Blocking NOS activity with L-NAME prevented TNF-alpha-induced NO generation by osteoclasts and the osteoclast survival stimulated by TNF-alpha. The iNOS selective inhibitor L-NIL also suppressed TNF-alpha-induced osteoclast survival, whereas low concentrations of NO releaser NOC-18 were sufficient to promote osteoclast survival. Furthermore, antiapoptotic and caspase suppressive effects of TNF-alpha on osteoclasts were abolished by L-NAME. Our findings indicate that iNOS-dependent NO generation contributes to the survival-promoting function of TNF-alpha in osteoclasts.
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PMID:Involvement of iNOS-dependent NO production in the stimulation of osteoclast survival by TNF-alpha. 1526 85

Blood flow changes in response to N-methyl-D-aspartate (NMDA) receptor activation were assessed using a laser Doppler flowmeter. Treatment of the joint with NMDA (1 mM; 0.1 ml) resulted in a significant increase in blood flow while the control phosphate buffer (PB) injection (0.1 M; pH 7.4) had no effect. Blocking NMDA receptors with the antagonist MK 801 (0.1 mM) prevented the increase in blood flow observed following NMDA injection, suggesting specificity of action. The NMDA-evoked vasodilation has been shown to be mediated through activation of several intracellular signaling transduction molecules, namely nitric oxide, release of calcitonin gene-related peptide (CGRP) and CAM kinase II. Blocking actions of these molecules with L-NAME (10 mg/ml), CGRP(8-37) (0.01 mM) and KN-93 (1 microM), respectively, prevented the increase in blood flow induced by NMDA in the present study. These results provide new evidence implicating NMDA receptors in knee joint inflammatory responses.
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PMID:NMDA receptors and associated signaling pathways: a role in knee joint blood flow regulation. 1536 62


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