UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inositol phosphate hydrolyzing activity of human phospholipase Cdelta1 (PLCdelta1) is markedly inhibited when the enzyme is coexpressed with the human heart G(h)/transglutaminase (TG) in human embryonic kidney cells. Because the cotransfection does not affect the amount of PLCdelta1 in the cells, the depression of phospholipase activity probably is a result of a direct interaction between the two proteins. An ELISA procedure was employed to document the associations of purified TG preparations from a variety of tissues (human red cells, rabbit lens, guinea pig liver) with PLCdelta1. Nucleotides (GTP > GDP > ATP > GMP = ADP, in order of decreasing efficiency) interfered with the formation of the PLCdelta1:TG complex. A conformational change in the TG partner, occurring with nucleotide binding, is thought to be responsible for dissociating the two proteins. The structural rearrangement produces a remarkable shift in the anodic mobility of TG in electrophoresis: TG(slow) + GTP -->/<-- [TG:GTP](fast). Altogether, our findings indicate that GTP controls PLCdelta1 activity by releasing this protein from an inhibitory association with G(h)/transglutaminase.
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PMID:Interactions of G(h)/transglutaminase with phospholipase Cdelta1 and with GTP. 1051 33

The effects of interleukin-1 beta (IL-1 beta) on the membrane potential and synaptic transmission were examined in neurons of mammalian pelvic ganglia. Bath-application of recombinant human IL-1 beta (6-300 pM) for 10 s-5 min produced a long-lasting hyperpolarization associated with increased input resistance in 11 neurons of rat major pelvic ganglia (MPG). In other 8 neurons, IL-1 beta (300 pM) produced a biphasic response that consists of an initial depolarization followed by a long-lasting hyperpolarization. IL-1 beta 163-171 (10-100 pM), a synthetic nonapeptide analog that contains the active domain of human IL-1 beta, mimicked the effect of IL-1 beta in MPG neurons. gamma-Aminobutyric acid (GABA, 300 microM) produced a depolarization followed by a hyperpolarization that was blocked by picrotoxin (100 microM). Db-cyclic guanosine monophosphate (db-cyclic GMP, 100 microM) also produced an initial depolarization followed by a long-lasting hyperpolarization. These results suggest that the IL-1 beta-induced biphasic response is mediated by a GABA receptor-cyclic GMP pathway. IL-1 beta and IL-1 beta 163-171 caused an initial facilitation followed by a long-lasting depression of the excitatory postsynaptic potential (EPSP) in rabbit VPG. The data suggest that IL-1 beta presynaptically depressed the EPSP by reducing the release of acetylcholine (ACh) from the pelvic nerve terminals.
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PMID:Effects of interleukin-1 beta on neurons in mammalian pelvic ganglia. 1065 89

Extracellular recording techniques were used to study the effects of the nitric oxide releasing agents diethylamine-NO (DEA-NO) and S-nitroso-N-acetyl-penicillamine (SNAP) on synaptic transmission in the intermediate and medial part of the hyperstriatum ventrale (IMHV), a part of the domestic chick forebrain that is essential for some forms of early learning. The field response evoked by local electrical stimulation was recorded in the IMHV in an in vitro slice preparation. DEA-NO (100-200 mgr) significantly depressed the field response in a concentration dependent and reversible manner. However, the depression produced by perfusion with 400 mgr DEA-NO, was not reversed following washout of the drug. With 400 mgr DEA-NO, NO reaches a maximum concentration of 10 mgr at 2 min of perfusion, and then declines slowly. SNAP (400 mgr) produced an effect similar to 400 mgr DEA-NO. Neither the immediate nor the longer-term depressive effect of NO is mediated by activation of guanylyl cyclase because in the presence of both low and high doses of ODQ, a potent and selective inhibitor of NO-stimulated guanylyl cyclase, NO produced the same depression of the field response. There is evidence however that the IMHV possesses c-GMP responsive elements since direct perfusion of 8-Br-cGMP (1 mM) produced a long-term but not an immediate depression. The long-term depression produced by 400 mgr DEA-NO was eliminated in the presence of either a selective adenosine A(1) receptor antagonist or an ADP-ribosyltransferase inhibitor. It was also possible to prevent the long-term effect in the presence of tetraethyl ammonium a K(+)-channel blocker. These results suggest that the NO may be acting presynaptically in a synergistic fashion with the adenosine A(1) receptor to depress transmitter release.
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PMID:Effects of nitric oxide release in an area of the chick forebrain which is essential for early learning. 1083 95

This study examined the effect of GMP in two models of depression in mice. The immobility times in the forced swimming test (FST) and in the tail suspension test (TST) were significantly reduced by GMP (dose range: 5-50 mg/kg and 5-100 mg/kg, i.p., respectively), without accompanying changes in ambulation in an open-field. I.c.v. injection of GMP (320-480 nmol/site) also reduced the immobility in the FST without affecting ambulation. The immobility of mice treated with MK-801 (0.01 mg/kg) + GMP (50 mg/kg) was not significantly different from the result obtained with MK-801 or GMP alone, but GMP (or MK-801) + imipramine (15 mg/kg) treatment induced a stronger effect in FST than administration of either drug alone. Pretreatment with p-chlorophenylalanine (100 mg/kg, 4 days) completely blocked the anti-immobility effect of GMP, MK-801 or fluoxetine (32 mg/kg), but only partially that of imipramine in the FST. The results suggest that the antidepressant-like effects produced by the administration of GMP, like MK-801, may be due to an indirect serotonin activation resulting from blockade of NMDA receptors.
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PMID:Acute treatments with GMP produce antidepressant-like effects in mice. 1088 29

The gas NO is a messenger that modulates neuronal function. The use of NO donors and NO synthase inhibitors as pharmacological tools revealed that this free radical is probably implicated in the regulation of excitability and firing, in long-term potentiation and long-term depression, as well as in memory processes. Moreover, NO modulates neurotransmitter release. In vivo and in vitro studies have shown that, in all brain structures investigated, endogenous NO modulates the release of several neurotransmitters, such as acetylcholine, catecholamines, excitatory and inhibitory amino acids, serotonin, histamine, and adenosine. In most cases, enhanced NO level in the tissue increases the release of neurotransmitters, although decreasing effects have also been observed. Cyclic 3'-5' guanosine monophosphate and glutamate mediate the modulation of transmitter release by NO. Recent observations suggest that the release of some transmitters is dually influenced by NO. Thus, besides modulation by presynaptically located auto- and heteroreceptors, NO released from nitrergic neurons seems to play a universal role in modulating the release of transmitters in the brain.
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PMID:Nitric oxide as modulator of neuronal function. 1125 62

The antidepressant-like effect of the hydroalcoholic extract obtained from aerial parts of Siphocampylus verticillatus, a Brazilian medicinal plant, was investigated in two models of depression in mice and against synaptosomal uptake of serotonin, noradrenaline and dopamine. The immobility times in the forced swimming test (FST) and in the tail suspension test (TST) were significantly reduced by the extract (dose range 100-1000 mg/kg, i.p.), without accompanying changes in ambulation when assessed in an open-field. In addition when given orally the extract was also effective in reducing the immobility time in the TST. The efficacy of extract in the TST was comparable to that of the tricyclic antidepressant imipramine (15 mg/kg, i.p.) and with fluoxetine (32 mg/kg, i.p.). The anti-immobility effect of the extract (600 mg/kg, i.p.) assessed in the TST was not affected by pre-treatment with naloxone (1 mg/kg, i.p., a non-selective opioid receptor antagonist) or L-arginine (750 mg/kg, i.p., a nitric oxide precursor). In contrast, the extract (600 mg/kg, i.p.) antidepressant-like effect was significantly reduced by pre-treatment of animals with p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis), sulpiride (50 mg/kg, i.p., a selective D2 receptor antagonist), prazosin (62.5 microg/kg, i.p., an alpha1 adrenoreceptor antagonist) or by guanosine 5'-monophosphate (GMP, 250 mg/kg, i.p., a nucleotide known to block some actions elicited by NMDA). The biochemical data show that the extract of S. verticillatus inhibited in a graded manner the uptake of monoamines. However, at the IC50 level, the extract was approximately 3.2 to 3.4-fold more potent and also more efficacious in inhibiting the synaptosomal uptake of noradrenaline and serotonin than dopamine. Taken together these data demonstrate that the extract of S. verticillatus elicited a significant antidepressant-like effect, when assessed in the TST and FST in mice. Its action seems to involve an interaction with adrenergic, dopaminergic, glutamatergic and serotonergic systems.
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PMID:Involvement of monoaminergic system in the antidepressant-like effect of the hydroalcoholic extract of Siphocampylus verticillatus. 1188 77

We report the identification of a compound whose K+-induced Ca2+-dependent release in rat cerebellar slices was reduced following climbing fibre deprivation by 3-acetylpyridine (3-AP) treatment. Based on HPLC retention time, UV absorption spectrum, and mass spectrometry, this compound was identified as adenosine. The K+-induced, Ca2+-dependent release of adenosine was subsequently quantified in control and 3-AP-treated rats. It decreased by 60 - 70% in both the cerebellar vermis and hemispheres following climbing fibre deprivation, while 3-AP treatment had no effect on adenosine release in the cerebral cortex. Inhibition of ecto-5'-nucleotidase by alpha,beta-methylene ADP and GMP decreased basal and stimulated efflux of adenosine in the cerebellum by 50 - 60%, indicating that a significant proportion of adenosine was derived from the extracellular metabolism of released nucleotides. Taken with the reports of other groups on adenosine in cerebellum, these results suggest that climbing fibre activity increases the extracellular level of adenosine, probably through the metabolism of released nucleotides. This adenosine could then cause presynaptic inhibition of the release of the parallel fibre transmitter, which is presumably glutamate. This may account for the climbing fibre-evoked depression of Purkinje cell sensitivity to parallel fibre input.
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PMID:Effect of Climbing Fibre Deprivation on the K+-evoked Release of Endogenous Adenosine from Rat Cerebellar Slices. 1210 18

We describe the case of a patient who came to our attention because of a reversible depression of myocardial contractility, probably due to myocarditis. A positron emission tomography study showed, in correspondence to the malfunctioning segments, a decreased F18-2-fluoro-2-deoxyglucose (F18-FDG) uptake in the presence of a normal perfusion as assessed by means of N13-labeled ammonia uptake. This phenomenon, called "reverse mismatch", shows that viability is not always dependent on FDG uptake and that it could be associated with the recovery of myocardial contractility. Some interpretations of the association between a reversible dysfunction and a reduced myocardial glucose metabolism are presented. The central role of nitric oxide and of cyclic guanosine monophosphate is hypothesized to explain both the mechanical and metabolic abnormalities.
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PMID:Evidence of reverse mismatch with positron emission tomography imaging in a patient with reversible myocardial dysfunction. 1247 22

We observed changes in cochlear blood flow (CoBF), abdominal blood flow (AbBF) and auricular blood flow (AuBF) in rats after administration of the nitric oxide (NO) synthase inhibitor N-nitro-L-arginine-methyl ester (L-NAME). Ten min after i.v. infusion of L-NAME, L-arginine, a substrate of NO, was infused (100 mg/kg) intravenously. Using a laser Doppler flowmeter, changes in blood flow were recorded from the basal turn of the right cochlea, abdominal wall or right auricle, and systemic blood pressure (BP) was recorded simultaneously from the left femoral artery. As another parameter of vascular response, vascular conductance (VC) was calculated from blood flow/mean BP. I.v. infusion of L-NAME produced a dose-dependent depression of cochlear VC at concentrations of 0.2 (-18.9%), 1 (-37.9%), 5 (-45.8%) and 10 mg/kg (-48.3%). Infusion of L-arginine partially reversed the decrease of CoBF caused by L-NAME. The group that received a 0.2 mg/kg infusion of L-NAME showed the largest degree of recovery (23.8%) with L-arginine, while the 10 mg/kg group showed the smallest degree of recovery (10.1%). AbBF also decreased after infusion of L-NAME (5 mg/kg) but to a lesser degree (-41.1% depression of VC) and with no significance compared to the decrease in CoBF (5 mg/kg L-NAME). Likewise, AuBF showed a decrease (-44.0% depression of VC) after infusion of L-NAME (10 mg/kg), the decrease being less than that of CoBF (10 mg/kg L-NAME). Recoveries from these decreased levels of VC in the AbBF and AuBF groups appeared to be smaller than those in the CoBF groups at the same dose of L-NAME (5.5% vs 17.3% in abdominal VC; 5.3% vs 10.1% in auricular VC). In a previous study comparing the CoBF changes caused by i.v. infusion and round window application of L-NAME, we proposed that i.v. infusion of L-NAME in rats primarily affects the precapillary arteriole of the spiral modiolar artery, which effectively regulates cochlear microcirculation as a resistance artery. Thus we assume that there may exist an active pathway of the NO/soluble guanylate cyclase/cyclic guanosine monophosphate system in the above vessels. With regard to the finding of a smaller recovery of VC with L-arginine in both the AbBF and AuBF groups, we consider that differences in L-arginine availability or uptake, and in the synthesis of NO, may exist between the cochlear and cutaneous vasculatures.
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PMID:Decrease in cochlear blood flow with infusion of nitric oxide synthase inhibitor and its recovery with L-arginine infusion: comparison with abdominal blood flow and auricular blood flow. 1254 97

Cortical spreading depression (CSD) is characterised by slowly propagating waves of cellular depolarization and depression and involves transient changes in blood flow, ion balance and metabolism. In cerebral ischaemia, peri-infarct CSD-like depolarization potentiates infarct growth, whereas preconditioning with a CSD episode protects against subsequent ischaemic insult. Thus, many of the long-lasting molecular changes that occur in CSD-affected tissue are presumed to be part of a 'neuroprotective cascade.' 3',5'-Cyclic guanosine monophosphate (cGMP) has been shown to be a neuroprotective mediator and the nitric oxide system, which increases cGMP production by soluble guanylate cyclase, is up-regulated by CSD. Atrial and C-type natriuretic peptide (ANP/CNP) are present in cerebral cortex and their actions are mediated via particulate guanylate cyclase receptors and cGMP production. Therefore, in further efforts to characterise the role of cGMP-related systems in CSD and neuroprotection, this study investigated possible changes in cortical natriuretic peptide expression following acute, unilateral CSD in rats. Using in situ hybridisation, significant 20-80% increases in ANP mRNA were detected in layers II and VI of ipsilateral cortex at 6 h and 1-14 days after CSD. Ipsilateral cortical levels were again equivalent to control contralateral values after 28 days. Assessment of cortical concentrations of ANP immunoreactivity by radioimmunoassay revealed a significant 57% increase at 7 days after CSD. Despite using a sensitive signal-amplification protocol, authentic ANP-like immunostaining was readily detected in subcortical nerve fibres, but was not reliably detected in normal or CSD-affected neocortex, suggesting the presence of very low levels, and/or active or differential processing of the peptide. Cortical CNP mRNA levels are not altered by CSD, indicating the specificity of the observed effects.Overall, these novel findings demonstrate a prolonged increase in cortical ANP expression after an acute episode of CSD. The overlap between the described time course of CSD-induced protection against ischaemic insult and demonstrated increases in ANP levels, suggest that ANP (like nitric oxide) may contribute to CSD-induced neuroprotection, via effects on cGMP production and other signal-transduction pathways.
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PMID:Atrial natriuretic peptide expression is increased in rat cerebral cortex following spreading depression: possible contribution to sd-induced neuroprotection. 1271 Sep 79

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