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)

To study the sequence of degenerative events possibly associated with cholinergic cell death in Alzheimer's disease, septal cholinergic neurons derived from rat embryonic brains were exposed to chronic excitotoxic stress by glutamate. Counts of choline acetyltransferase (ChAT)-immunopositive neurons and measurement of ChAT activity revealed that concentrations of glutamate on the order of 70 microM killed 50% of cholinergic neurons after 24 hr of treatment. Neurotoxic effects were not aimed at cholinergic neurons specifically, since other populations of cells present in these cultures were also affected at similar concentrations. The noncompetitive N-methyl-D-aspartate (NMDA) receptor channel antagonist MK-801 (10 microM) abolished acute neuronal swelling and rescued from late degeneration both cholinergic and noncholinergic cells when concentrations of glutamate up to 500 microM were added to the cultures. Protective effects declined progressively with increasing concentrations of the amino acid, even when MK-801 was raised to its highest nontoxic levels, e.g., 50 microM. the kainate/quisqualate receptor antagonist CNQX provided no protection alone or in combination with MK-801. Nerve growth factor (NGF), used in standard culture conditions to stimulate the expression of the cholinergic phenotype, was shown not to influence excitotoxic neurodegenerative changes. Several observations suggested that nitric oxide (NO) may act as an intercellular messenger of NMDA-mediated cell death in septal cultures: 1) Most of the cholinergic neurons contained the NO synthase enzyme as characterized by NADPH-diaphorase (NADPH-d) staining; 2) sodium nitroprusside (SNP) [a chemical with the ability of generating NO] was capable of mimicking some of the aspects of the glutamate-induced degenerative process; 3) the rise in cyclic GMP which was observed in the presence of toxic levels of glutamate and which is usually taken as an index of NO production, was antagonized by MK-801 and by the inhibitor of the NO synthase enzyme, L-NOARG. Yet, the fact that L-NOARG and its congener, L-NAME, were ineffective in preventing glutamate-induced neurodegenerative changes in our culture system did not substantiate our working hypothesis. Altogether these results suggest that glutamate-induced cholinergic neuronal death is the consequence of an overstimulation of NMDA receptors and that neither NGF nor NO plays a key role in the degenerative process.
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PMID:Death of septal cholinergic neurons produced by chronic exposure to glutamate is prevented by the noncompetitive NMDA receptor/channel antagonist, MK-801: role of nerve growth factor and nitric oxide. 762 90

Nitric oxide (NO) is a candidate retrograde messenger involved in synaptic plasticity, and is linked to the cholinergic system in the brain. We examined the role of NO in the acquisition of visual and spatial discriminations by daily administration of either saline or 1-nitroarginine methyl ester (L-NAME), an NO synthase inhibitor. Brains were assayed for NO synthase activity and two presynaptic cholinergic markers: hemicholinium-3 (HC-3) binding, which determines the number of sodium-dependent high-affinity choline uptake sites, and activity of choline acetyltransferase (ChAT), which is the synthetic enzyme for acetylcholine. In both behavioral tasks, the acquisition rate was not different between groups. L-NAME reduced NO synthase activity by 85% in all brain areas assayed and HC-3 binding by 38% in hippocampus and 48% in posterior cortex. ChAT activity was not different between groups in any region assayed. These data suggest that NO does not play a role in visual or spatial discrimination learning. However, NO synthase inhibition may play a role in the regulation of cholinergic activity.
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PMID:Nitric oxide synthase inhibition does not impair visual or spatial discrimination learning. 897 42

Oesophageal peristalsis is controlled by vagal motor neurones, and intrinsic neurones have been identified in the striated muscle oesophagus. However, the effect(s) of intrinsic neurones on vagally mediated contractions of oesophageal striated muscles has not been defined. The present study was designed to investigate the role of intrinsic neurones on vagally evoked contractions of oesophageal striated muscles, using hamster oesophageal strips maintained in an organ bath. Stimulation (30 micros, 20 V) of the vagus nerve trunk produced twitch contractions. Piperine inhibited vagally evoked contractions, while capsaicin and NG-nitro-L-arginine methyl ester (L-NAME) abolished the inhibitory effect of piperine. The effect of L-NAME was reversed by subsequent addition of L-arginine, but not by D-arginine. L-NAME did not have any effect on the vagally mediated contractions and presumed 3H-ACh release. NONOate, a nitric oxide donor, and dibutyryl cyclic GMP inhibited twitch contractions. Inhibition of vagally evoked contractions by piperine and NONOate was fully reversed by ODQ, an inhibitor of guanylate cyclase. Immunohistochemical staining showed immunoreactivity for nitric oxide synthase (NOS) in nerve cell bodies and fibres in the myenteric plexus and the presence of choline acetyltransferase and NOS in the motor endplates. Only a few NOS-immunoreactive portions in the myenteric plexus showed vanilloid receptor 1 (VR1) immunoreactivity. Our results suggest that there is a local neural reflex that involves capsaicin-sensitive neurones, nitrergic myenteric neurones and vagal motor neurones.
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PMID:Role of intrinsic nitrergic neurones on vagally mediated striated muscle contractions in the hamster oesophagus. 1281 49

The dorsal motor nucleus of the vagus (DMV) contains preganglionic neurons that control gastric motility and secretion. Stimulation of different parts of the DMV results in a decrease or an increase in gastric motor activities, suggesting a spatial organization of vagal preganglionic neurons in the DMV. Little is known about how these preganglionic neurons in the DMV synapse with different groups of intragastric motor neurons to mediate contraction or relaxation of the stomach. We used pharmacological and immunohistochemical methods to characterize intragastric neural pathways involved in mediating gastric contraction and relaxation in rats. Microinjections of L-glutamate (L-Glu) into the rostral or caudal DMV produced gastric contraction and relaxation, respectively, in a dose-related manner. Intravenous infusion of hexamethonium blocked these actions, suggesting mediation via preganglionic cholinergic pathways. Atropine inhibited gastric contraction by 85.5 +/- 4.5%. Gastric relaxation was reduced by intravenous administration of N(G)-nitro-L-arginine methyl ester (L-NAME; 52.5 +/- 11.9%) or VIP antagonist (56.3 +/- 14.9%). Combined administration of L-NAME and VIP antagonist inhibited gastric relaxation evoked by L-Glu (87.8 +/- 4.3%). Immunohistochemical studies demonstrated choline acetyltransferase immunoreactivity in response to L-Glu microinjection into the rostral DMV in 88% of c-Fos-positive intragastric myenteric neurons. Microinjection of L-Glu into the caudal DMV evoked expression of nitric oxide (NO) synthase and VIP immunoreactivity in 81 and 39%, respectively, of all c-Fos-positive intragastric myenteric neurons. These data indicate spatial organization of the DMV. Depending on the location, microinjection of L-Glu into the DMV may stimulate intragastric myenteric cholinergic neurons or NO/VIP neurons to mediate gastric contraction and relaxation.
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PMID:Spatial organization of neurons in the dorsal motor nucleus of the vagus synapsing with intragastric cholinergic and nitric oxide/VIP neurons in the rat. 1846 Jun 97

Profound changes in intestinal motility occur during the postnatal period, but the involvement of the enteric nervous system (ENS), a key regulator of gastrointestinal (GI) motility, in these modifications remains largely unknown. We therefore investigated the postnatal development of the ENS phenotype and determined its functional repercussion on the neuromuscular transmission in the rat colon. Sprague-Dawley rats were euthanized at postnatal day (P) 1, P3, P5, P7, P14, P21, and P36. Whole mounts of colonic myenteric plexus were stained with antibodies against choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and HuC/D. Colonic contractile response induced by electrical field stimulation (EFS) was investigated in organ chambers in absence or presence of N-nitro-l-arginine methyl ester (l-NAME) and/or atropine. In vivo motility was assessed by measurement of the colonic bead latency time. Randomly occurring ex vivo contractions appeared starting at P5. Starting at P14, rhythmic phasic contractions occurred whose frequency and amplitude increased over time. In vivo, bead latency was significantly reduced between P14 and P21. Ex vivo, EFS-induced contractile responses increased significantly over time and were significantly reduced by atropine starting at P14 but were sensitive to l-NAME only after P21. The proportion of ChAT-immunoreactive (IR) neurons increased time dependently starting at P14. The proportion of nNOS-IR neurons increased as early as P5 compared with P1 but did not change afterward. Our data support a key role for cholinergic myenteric pathways in the development of postnatal motility and further identify them as putative therapeutic target for the treatment of GI motility disorders in the newborn.
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PMID:Postnatal development of myenteric neurochemical phenotype and impact on neuromuscular transmission in the rat colon. 2052 37

The expression of apelin and its receptors (APJ) in central autonomic networks suggests that apelin may regulate gastrointestinal motor functions. In rodents, central administration of apelin-13 has been shown to inhibit gastric emptying; however, the mechanisms involved remain to be determined. Using male adult Sprague-Dawley rats, the aims of the present study were 1) to determine the expression of APJ receptor in the dorsal vagal complex (DVC), 2) to assess the effects of central application of apelin-13 into the DVC on gastric tone and motility, and 3) to investigate the neuronal pathways responsible for apelin-induced alterations. APJ receptor immunoreactivity was detected in gastric-projecting and choline acetyltransferase-positive neurons of the DVC. Microinjection of apelin-13 into the DVC significantly decreased gastric tone and motility in both corpus and antrum. The apelin-induced reduction in gastric tone and motility was prevented by surgical vagotomy or fourth ventricular application of the APJ receptor antagonist, [Ala13]apelin-13 (F13A). Systemic administration of the muscarinic receptor antagonist atropine, but not the nitric oxide synthase inhibitor nitro-l-arginine methyl ester (l-NAME), abolished the apelin-induced inhibitory responses. The present results indicate a central modulatory role of apelin in the vagal neurocircuitry that controls gastric motor functions via withdrawal of the tonically active cholinergic pathway. NEW & NOTEWORTHY This is the first study investigating the effects induced by brain stem application of apelin-13 while monitoring gastric tone and motility in rats. We have found that gastric-projecting neurons of the dorsal vagal complex express apelin receptors (APJ), which mediate the inhibitory actions of apelin-13. The inhibitory effects of apelin were abolished by systemic preadministration of atropine, but not nitro-l-arginine methyl ester (l-NAME). Apelin seems to modulate gastric motility via withdrawal of the tonically active vagal cholinergic pathway.
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PMID:Apelin-13 inhibits gastric motility through vagal cholinergic pathway in rats. 2902 30