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)

The objective of the present study was to investigate the potential role of the free radical nitric oxide (NO) in the development of fetal rat mesencephalic neurons grafted in a 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease. First, using nitric oxide synthase (NOS)-immunocytochemistry and reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry, we investigated the presence of the neuronal isoform of NOS (nNOS) in intrastriatal mesencephalic grafts. During the course of the experiment (16 weeks) an increase in the staining intensity and the number of nNOS/NADPH-d positive cells within the grafts was observed, as well as a gradual maturation of dopaminergic neurons. In addition, within both the host striatal and grafted mesencephalic tissue, a NO-dependent accumulation of cyclic guanosine monophosphate (cGMP) was detected, indicating the presence of guanylate cyclase, i.e., the target-enzyme for NO. Secondly, to determine the impact of NO on the survival of grafted dopaminergic neurons, 6-OHDA lesioned rats received mesencephalic grafts and were subsequently treated with the competitive NOS-inhibitor Nomega-nitro-l-arginine methylester (l-NAME). After chronic treatment for 4 weeks, tyrosine hydroxylase immunocytochemistry revealed no apparent differences between the survival of grafted dopaminergic neurons in control- or l-NAME treated animals, respectively. As the maturation of grafted dopaminergic neurons coincides with a gradual increase in the expression of nNOS within the graft and since dopaminergic cell numbers are not changed upon administration of l-NAME, it is concluded that endogenously produced and potentially toxic NO does not affect the survival of grafted fetal dopaminergic neurons.
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PMID:Sustained pharmacological inhibition of nitric oxide synthase does not affect the survival of intrastriatal rat fetal mesencephalic transplants. 959 18

The present study was designed to examine the role of nitric oxide (NO) in quinolinic acid (QUIN)-induced depletion of rat striatal nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase and enkephalinergic neurons. Intrastriatal injection of QUIN produced a dose-dependent decrease in NADPH diaphorase and enkephalin positive cells, with cell loss being evident following the injection of 6 and 18 nmol QUIN, respectively. To evaluate the role of NO in QUIN-induced toxicity, animals were pretreated with the non-specific nitric oxide synthase (NOS) inhibitor, Nomega-nitro-l-arginine (l-NAME) or the selective neuronal NOS inhibitor, 7-nitro indazole (7-NI). l-NAME (2x250 mg/kg, i.p. 8 h apart) maximally inhibited striatal NOS activity by 85%, while 7-NI (50 mg/kg, i.p.) maximally inhibited striatal NOS activity by 60%. Pretreatment with l-NAME or 7-NI potentiated the loss of NADPH diaphorase neurons resulting from intrastriatal injection of low doses of QUIN (18 nmol). Neither NOS inhibitor had any effect on the loss of striatal NADPH diaphorase neurons induced by a higher dose of QUIN (24 nmol). In contrast, 7-NI partially prevented the QUIN (18 and 24 nmol)-induced loss of enkephalinergic neurons, while l-NAME had no effect. These results indicate that NO formation may play a role in QUIN-induced loss of enkephalinergic neurons, but not in the loss of NADPH diaphorase neurons.
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PMID:Modulation of quinolinic acid-induced depletion of striatal NADPH diaphorase and enkephalinergic neurons by inhibition of nitric oxide synthase. 988 56

This study examined a possible functional involvement of nitric oxide (NO) in the median eminence (ME) and arcuate nucleus (ARC) after capsaicin treatment in rats. Subcutaneous injection of capsaicin increased nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity in the ARC-ME compared with vehicle treatment. Fos expression was increased in the ARC after capsaicin injection compared with vehicle-treated rats. Pretreatment with the NO synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME) attenuated the effect of capsaicin on Fos expression and NADPH-d reactivity in the ARC-ME in comparison with rats injected with D-NAME, the inactive stereoisomer of L-NAME. These observations suggest that NO makes a major contribution to the response of the ARC-ME to a stressor such as capsaicin.
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PMID:A role for nitric oxide in the median eminence and arcuate nucleus response to capsaicin treatment in rats. 1036 26

Nitric oxide (NO) may subserve different functions in different central neurons subjected to axotomy. The difference may depend on whether the neurons basally express neuronal nitric oxide synthase (nNOS), a biosynthetic enzyme of NO. This is supported by our previous finding that suggests the differential role of NO in neurons of nucleus dorsalis (ND) and red nucleus (RN) which have different basal expression of nNOS. This study aimed to establish firmly the functions of NO, as revealed by nNOS immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry, by the administration of endogenous NO donor, l-arginine (l-arg), and NOS inhibitor, l-N(G)-nitroarginine methyl ester (l-NAME). To relate the role of NO to glutamate receptors (GluR), the distributions of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-d-aspartate receptor (NMDAR) in the two nuclei were revealed by immunohistochemical techniques. nNOS immunoreactivity was void in ND neurons, but expressed weakly in the RN normally. It was induced in ipsilateral ND neurons and upregulated on both sides of RN after spinal cord hemisection. Neuronal loss in the ipsilateral ND was augmented by l-arg, but reduced by l-NAME. In the contralateral RN, l-arg attenuated neuronal loss. NMDAR1 was present in most neurons in ND. After axotomy, some NMDAR1 immunoreactive neurons of the ipsilateral ND were induced to express NOS, whereas RN neurons showed strong staining for NMDAR1 and all the AMPA subunits. Most of the NOS-positive neurons in the RN were coexistent with GluR2 in normal rats and those subjected to axotomy. The present data demonstrated that NO exerted neurodestructive function in the non-NOS-containing ND neurons characterized by NMDAR as the predominant glutamate receptor. NO might be beneficial to the NOS-containing RN neurons. This could be attributed to the presence of GluR2. Possible diverse synthesizing pathways of NO in two different central nuclei were suggested from the observation that NOS was colocalized with NADPH-d in ND neurons, but not in RN neurons.
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PMID:Neuroprotective and neurodestructive functions of nitric oxide after spinal cord hemisection. 1068 69

Although capsaicin has been shown to activate certain neuronal groups in the hypothalamus and amygdala, the neurotransmitters involved and the exact mechanism of action are not clearly understood at present. The aim of this study was to examine the hypothesis that the effect of capsaicin in the rat hypothalamus and amygdala primarily involves direct activation of the endogenous nitric oxide synthase (NOS) neurons responsible for the synthesis of nitric oxide (NO). Subcutaneous capsaicin injection in male rats, compared with vehicle, caused a significant increase in Fos expression in the paraventricular nucleus (PVN), supraoptic nucleus (SON), and medial and cortical amygdala. The expression of nicotinamide adenine dinucleotide phosphate diaphorase, a histochemical marker for NOS, was also increased in these brain areas in addition to the periventricular and lateral hypothalamic area and central amygdaloid nucleus. Also, capsaicin significantly increased the expression of neuronal NOS messenger RNA and protein in the PVN, SON, and medial amygdala as demonstrated by in situ hybridization and immunohistochemistry, respectively. A higher proportion of the NOS neurons in the PVN, periventricular region, SON and amygdala showed Fos expression in response to capsaicin than vehicle injection. There was little, if any, Fos activation in the NOS-positive neurons in the lateral hypothalamic area. The capsaicin-induced activation of the hypothalamic PVN and SON neurons and the medial amygdaloid nucleus was attenuated in the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) -pretreated animals in comparison with the inactive enantiomer D-NAME. These observations indicate that activation of the endogenous NOS system and production of NO constitute a major pathway through which capsaicin exerts its effect within the hypothalamus and amygdala.
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PMID:Importance of endogenous nitric oxide synthase in the rat hypothalamus and amygdala in mediating the response to capsaicin. 1088 Sep 96

In this study, we examined the effect of acute capsaicin injection on nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d, a histochemical index of nitric oxide, NO, synthase) and Fos expression in the rat pituitary gland. Compared with vehicle, capsaicin significantly activated Fos expression in the anterior and intermediate lobes. In addition, capsaicin-treated rats showed a significant upregulation of NADPH-d in the anterior and neural lobes. Pretreatment of the animals with a specific NO synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), significantly attenuated the capsaicin-induced Fos expression in the anterior and intermediate lobes. These observations suggest that NO is a key regulator of the acute effect of capsaicin on the pituitary gland.
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PMID:Fos activation and upregulation of nicotinamide adenine dinucleotide phosphate diaphorase in the rat pituitary by acute capsaicin injection. 1109 Sep 77

We have examined nerve growth factor (NGF)-triggered signaling in two NIH3T3 cell lines exogenously expressing the NGF receptor, TrkA. TRK1 cells cease to proliferate and extend long processes in response to NGF, while E25 cells continue to proliferate in the presence of NGF. These two cell lines express similar levels of TrkA and respond to NGF with rapid elevation of mitogen-activated protein kinase (MAPK) activity. MAPK activation is slightly more sustained for E25 cells than for TRK1 cells, although sustained activation of MAPK has been suggested to cause cell-cycle arrest. As judged by NADPH-diaphorase staining, nitric oxide synthase (NOS) activity is increased in TRK1 cells upon exposure to NGF. In contrast, diaphorase staining in E25 cells is unaffected by NGF treatment. Immunocytochemistry shows that levels of the brain NOS (bNOS) isoform are increased in TRK1, but not E25, cells exposed to NGF. Furthermore, Western blots show that NGF elevated cyclin-dependent kinase inhibitor, p21(WAF1), in TRK1 cells only. NGF-induced p21(WAF1) expression, cell-cycle arrest and process extension are abolished by N-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NOS. The inactive enantiomer, D-NAME, did not inhibit these responses. Furthermore, even though E25 cells do not respond to NGF or nitric oxide donors, they do undergo a morphological change in response to NGF plus a nitric oxide donor. Therefore, NOS and p21(WAF1) are induced only in the TrkA-expressing NIH3T3 cell line that undergoes cell-cycle arrest and morphological changes in response to NGF. These results demonstrate that sustained activation of MAPK is not the sole determining factor for NGF-induced cell-cycle arrest and implicate NO in the cascade of events leading to NGF-induced morphological changes and cell-cycle arrest.
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PMID:Cell-cycle arrest in TrkA-expressing NIH3T3 cells involves nitric oxide synthase. 1118 Apr 9

Entamoeba histolytica trophozoites were inoculated into the liver of hamsters and serum nitrate/nitrite levels [expressed as nitric oxide (NO) production] were determined at different times during amebic liver abscess (ALA) development. We also tested the effects of NO synthase (NOS) inhibitors such as N(G)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine, and dexamethasone during ALA production. Since NOS activity has been correlated with expression of reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) in tissues, we performed histochemistry studies to determine the activity of the latter in livers infected with E. histolytica trophozoites. Production of NO in serum was directly proportional to the size of ALAs, and NOS inhibitors caused low levels of NO and smaller ALAs. Our data suggest that NO does not have any lytic effect on E. histolytica trophozoites and is therefore incapable of providing protection against the amebic liver infection. In addition, NADPHd activity was detected histochemically in hepatocytes and inflammatory cells associated with focal necrosis containing trophozoites. The positive reactivity observed in these parasites may be attributable to a close biochemical similarity of NADPHd to the NADPH:flavin oxidoreductase described in E. histolytica by other investigators.
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PMID:Entamoeba histolytica: production of nitric oxide and in situ activity of NADPH diaphorase in amebic liver abscess of hamsters. 1119 49

1. The role of nitric oxide (NO) in central cardiovascular regulation and the correlation between NO and glutamate-induced mechanisms is not clear. Microinjection of glutamate (3 nmol/30 nL) into dorsomedial medulla (DM) and rostral ventrolateral medulla (RVLM) increased arterial blood pressure (BP) and sympathetic vertebral nerve activity (VNA). Thus, in the present study, we examined the modulation by NO of glutamate-induced pressor responses in the DM and RVLM of cats. 2. Histochemical methods using nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) as a marker to stain neurons containing NO synthase (NOS), showed positive findings of NOS in both the DM and RVLM. 3. Microinjection of N(G)-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, into the DM or RVLM did not alter resting BP and VNA, but it did cause a dose-dependent attenuation of glutamate-induced pressor responses. Interestingly, the increase in NO levels that resulted from pretreatment with L-arginine (L-Arg) or sodium nitroprusside (SNP) did not alter resting BP and VNA, but still inhibited glutamate-induced pressor responses in the DM and RVLM in a dose-dependent manner. 4. We also examined whether NO modulated the pressor responses induced by activation of different excitatory amino acid receptors. N-Methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) were used. Consistent with the results from the initial glutamate studies, we observed that not only L-NAME, but also L-Arg and SNP attenuated pressor responses induced by NMDA and AMPA. No difference was found between the effects of NO on NMDA- and AMPA-induced pressor responses. 5. To investigate the possibility of a loss of agonist selectivity, the effects of D-2-amino-5-phosphonovalerate (D-AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on AMPA and NMDA responses in the DM were examined. The results showed that CNQX did not alter NMDA-induced pressor responses, while D-AP5 failed to alter AMPA-induced responses. 6. Our results suggest that activation of the glutamate-induced pressor mechanism is regulated by changes in NO levels in the DM and RVLM. This implies that NO may play a permissive role to allow operation of the glutamate-activation mechanism.
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PMID:Role of nitric oxide on pressor mechanisms within the dorsomedial and rostral ventrolateral medulla in anaesthetized cats. 1120 69

Changes in enteric neurons containing various neurotransmitters in the colon have been described in diabetic rats; however, how these changes are related to colonic motility disorders remains unclear. Nitric oxide (NO) is known to be an important inhibitory neurotransmitter in the enteric nervous system. In the present study, we investigated the peristaltic reflex using our modified Trendelenburg's method to evaluate the differences in enteric nitrergic neurons of the distal colon between spontaneously diabetic rats and their sibling control rats. We measured maximum intraluminal pressure, threshold pressure and propagation distance of the reflex contraction. These diabetic rats showed a greater maximum intraluminal pressure than that in the control rats. NG nitro-L-arginine methyl ester (L-NAME) significantly increased the maximum pressure in the control rats. Although L-arginine did not change the maximum pressure, sodium nitroprusside (SNP) significantly decreased it in these diabetic rats. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase reactivities in the myenteric plexus were much weaker in the diabetic rats than those in the control rats. These results indicate that the colonic peristaltic reflex is enhanced by impairment of enteric nitrergic inhibitory neurons in spontaneously diabetic rats.
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PMID:Enhanced colonic peristalsis by impairment of nitrergic enteric neurons in spontaneously diabetic rats. 1157 Jul 5


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