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)

Studies have indicated the involvement of a glutamatergic mechanism in lithium (Li+) action. Glutamatergic agonists, such as kainic acid, are known to promote the synthesis of nitric oxide (NO) and to increase cGMP, while Li+ has displayed a similar, yet unexplained, ability to increase cGMP. NO synthesis is regarded as the principal prodromal event leading to the activation of the guanyl cyclase-cGMP transduction mechanism. In the present study, the involvement of the NO:cGMP pathway in the action of Li+ was examined, while the possibility of a glutamatergic mechanism in this response was also investigated. Parameters examined included cortical accumulation of cGMP and the stable oxidative metabolites of NO, viz. NO2- and NO3-, collectively expressed as NO2-. A significant positive correlation was observed in the in vivo cGMP and NO2- data throughout all the groups. Chronic treatment of rats with LiCl (0.3% m/m) engendered a significant increase in cGMP levels which was inhibited by the NO-synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME). Acute administration of kainic acid resulted in an increased accumulation of NO2-, also prevented by concomitant L-NAME administration. In addition, a synergistic stimulatory response on cortical NO2- was observed in the combination of LiCl and kainic acid. Collectively, these data implicate an involvement of a glutamatergic-mediated NO:cGMP transduction mechanism in the action of Li+.
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PMID:Evidence that lithium induces a glutamatergic: nitric oxide-mediated response in rat brain. 806 3

Erectile function (erection and detumescence) involves the complex interaction of direct neuronal stimulation of corporal smooth muscle, neurohumoral release of specific endothelial contractile and relaxant factors, and secondary modulation by a variety of putative neuropeptides and vasoactive modulators including nitric oxide. The specific aim of the current study was to determine the relative contribution of nitric oxide, adrenergic, purinergic, and cholinergic stimulation in the relaxant response to field stimulation. The results demonstrate that virtually all of the inhibitory effects of field-stimulated relaxation could be explained by the release of nitric oxide. L-NAME (L-NG-nitro arginine methyl ester, a competitive inhibitor of NO synthase) reduced field-stimulated relaxation by over 95% at all frequencies. Neither atropine nor propranolol (or the combination of the two) had any significant effect on field-stimulated relaxation. L-NAME blocked both field-stimulated relaxation and bethanechol-stimulated relaxation. However, methylene blue (a guanyl cyclase inhibitor) was significantly more potent at blocking bethanechol-stimulated relaxation than field-stimulated relaxation. Neither L-NAME nor methylene blue had any effect on nitroprusside (a direct liberator of NO) nor ATP-stimulated relaxation. Isoproterenol had only a minor inhibitory effect on phenylephrine-contracted tissue. These data suggest that 1) Methylene blue, which inhibits guanyl cyclase, is a relatively poor inhibitor of field-stimulated relaxation. 2) L-NAME is a potent inhibitor of NO synthesis and can in a dose-dependent fashion inhibit over 95% of field-stimulated relaxation. 3) Equipotent relaxation of corporal smooth muscle can be effected through pharmacologic stimulation with ATP (2 mM), nitroprusside (200 microM), and field stimulation (32 Hz).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative studies on rabbit corpus cavernosal contraction and relaxation. An in vitro study. 818 36

Intracellular Ca(2+) mobilization and release into mammal CSF plays a fundamental role in the etiogenesis of fever induced by the proinflammatory cytokine interleukin-1beta (IL-1beta) and other pyrogens. The source and mechanism of IL-1beta-induced intracellular Ca(2+) mobilization was investigated using two experimental models. IL-1beta (10 ng/ml) treatment of rat striatal slices preloaded with (45)Ca(2+) elicited a delayed (30 min) and sustained increase (125-150%) in spontaneous (45)Ca(2+) release that was potentiated by l-arginine (300 microm) and counteracted by N-omega-nitro-l-arginine methyl ester (l-NAME) (1 and 3 mm). The nitric oxide (NO) donors diethylamine/NO complex (sodium salt) (0.3 and 1 mm) and spermine/NO (0.1 and 0.3 mm) mimicked the effect of IL-1beta on Ca(2+) release. IL-1beta stimulated tissue cGMP concentration, and dibutyryl cGMP enhanced Ca(2+) release. The guanyl cyclase inhibitors 1H-[1,2, 4]oxadiazole[4,3-a] quinoxalin-1-one (100 microm) and 6-[phenylamino]-5,8 quinolinedione (50 microm) counteracted Ca(2+) release induced by 2.5 but not 10 ng/ml IL-1beta. Ruthenium red (50 microm) and, to a lesser extent, heparin (3 mg/ml) antagonized IL-1beta-induced Ca(2+) release, and both compounds administered together completely abolished this response. Similar results were obtained in human astrocytoma cells in which IL-1beta elicited a delayed (30 min) increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) (402 +/- 71.2% of baseline), which was abolished by 1 mm l-NAME. These data indicate that the NO/cGMP-signaling pathway is part of the intracellular mechanism transducing IL-1beta-evoked Ca(2+) mobilization in glial and striatal cells and that the ryanodine and the inositol-(1,4,5)-trisphosphate-sensitive Ca(2+) stores are involved.
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PMID:Nitric oxide modulation of interleukin-1[beta]-evoked intracellular Ca2+ release in human astrocytoma U-373 MG cells and brain striatal slices. 1112 73

The influence of nitric oxide (NO) on hypnotic activity of diazepam, chlordiazepoxide and clonazepam was studied in mice. Administration of both non-selective NO synthase inhibitors: N(G)-nitro-L-arginine methyl ester (L-NAME), N(G)-nitro-L-arginine (L-NOARG) and selective NO synthase inhibitor 7-nitroindazole (7-NI) resulted in significant increase in the duration of diazepam-, chlordiazepoxide- and clonazepam-induced sleep. The effects of co-administration of the examined inhibitors with benzodiazepines were not changed by L-arginine, a substrate for NO formation. Administration of L-arginine alone had no effect on the duration of sleep induced by benzodiazepines. Methylene blue, the guanyl cyclase inhibitor, was able to increase the duration of benzodiazepine-induced sleep. These findings suggest that the cGMP/NO system may participate in hypnotic effects of benzodiazepines.
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PMID:Involvement of nitricoxidergic system in the hypnotic effects of benzodiazepines in mice. 1566 84

Within the striatum, the gaseous neurotransmitter nitric oxide (NO) is produced by a subclass of interneurons containing the neuronal NO synthase (nNOS). NO promotes the second messenger cGMP through the activation of the soluble guanyl cyclase (sGC) and plays a crucial role in the integration of glutamate (GLU) and DA transmission. The aim of this study was to characterize the impact of 6-hydroxyDA (6-OHDA) lesion of the rat nigrostriatal pathway on NO/cGMP system. In vivo extracellular single units recordings were performed under urethane anesthesia to avoid any potentially misleading contributions of cortically-driven changes on endogenous NO. Hence, no electrical extrastriatal stimulation was performed and great attention was paid to the effects of 3-morpholinosydnonimine (SIN-1, a NO donor), N(G)-nitro-L-arginine methyl ester (L-NAME, a nonselective NOS inhibitor) and Zaprinast (a PDE inhibitor) delivered by iontophoresis upon the main striatal phenotypes. The latter were operationally distinguished in silent medium spiny-like neurons (MSN), with negligible spontaneous activity but displaying glutamate-induced firing discharge at rest and spontaneously active neurons (SAN), representing to a large extent nonprojecting interneurons. SANs were excited by SIN-1 and Zaprinast while MSNs showed a clear inhibition during local iontophoretic application of SIN-1 and Zaprinast. In 6-OHDA animals, SIN-1-induced excitation in SANs was significantly increased (on the contrary, the inhibitory effect of L-NAME was less effective). Interestingly, in DA-denervated animals, a subclass of MSNs (40%) displayed a peculiar excitatory response to SIN-1. These findings support the notion of an inhibitory modulatory role exerted by endogenous NO on control striatal projection cells. In addition, these findings suggest a functional cross-talk between NO, spontaneously active interneurons, and projection neurons that becomes critical in the parkinsonian state.
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PMID:In vivo electrophysiology of dopamine-denervated striatum: focus on the nitric oxide/cGMP signaling pathway. 1836 39

Two reactive oxygen species (ROS), nitric oxide (NO(.)) and superoxide ((.)O2), contribute to persistent pain. Using three different animal models where ROS mediate pain, this study examined whether NO(.) and (.)O2 converge to peroxynitrite (ONOO(-)) or whether each has an independent signaling pathway to produce hyperalgesia. The hyperalgesia after spinal nerve ligation was attenuated by removing (.)O2 by TEMPOL or inhibiting NO(.) production by L-NAME, but not by removing peroxynitrite with FeTMPyP. Nitric oxide-induced hyperalgesia was not affected by removing (.)O2 but was reduced by a guanyl cyclase inhibitor. Superoxide-induced hyperalgesia was not affected by inhibiting NO(.) production but was suppressed by a protein kinase C inhibitor. The data suggest that NO(.) and (.)O2 operate independently to generate pain.
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PMID:Superoxide signaling in pain is independent of nitric oxide signaling. 1979 17