Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Entry rates of acetate and oleate and their incorporation into lipids of blood plasma and fatty acids of milk were studied in lactating goats fed a concentrate-roughage ration with propionic acid infused intraruminally at 0, 5.52, and 13.74 g/h by primed constant intravenous infusion of [1-carbon-14] acetate and [9, 10-hydrogen-3] oleate. Means for infusion rates were acetate, 60, 52, and 39 micrograms/ml blood plasma; propionate 9, 12, and 22 micrograms/ml; oleate, 19, 14, and 12 micrograms/ml; acetate entry rate, 3.9, 2.7, and 1.8 mmol/h per kg bodyweight; oleate entry rate, 47, 29, and 19 mumol/h per kg bodyweight; acetate oxidation rate, 2.0, 1.7, and 1.4 mmol/h per kg, and its contribution to the total carbon dioxide production, 16, 14, and 11%. Propionic acid increased incorporation of carbon-14 and hydrogen-3 into plasma lipids, elevated proportions of 7:0, 9:0, 11:0, 13:0, 15:0, and 17:0 fatty acids in milk, and tended to lower others. Specific radioactivities of milk fatty acids during infusion of propionic acid were elevated by 1.8 to 2.8 times, and total fatty acids in milk and plasma were lowered by 22 and 38%. Data support the glucogenic theory that propionic acid either directly or through gluconeogenesis stimulates insulin secretion, which in turn inhibits release of fatty acids from adipose tissue, resulting in milk fat depression.
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PMID:Effect of propionic acid on kinetics of acetate and oleate and on plasma and milk fatty acid composition of goats. 674 42

Long term depression (LTD) of parallel fibre-Purkinje cell responses may result from desensitization of AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) type glutamate receptors, for which a cascade of reactions involving calcium, inositol-1,4,5-trisphosphate, nitric oxide (NO), guanosine-3'5'-monophosphate (cGMP) and protein kinases C and G has been previously proposed. The involvement of cGMP in synaptic LTD was confirmed by direct injection of cGMP and 8-bromo-cGMP (8-Br-cGMP) into the dendrites of Purkinje cells. Pairing injections with parallel fibre stimulation led to a LTD of synaptic transmission which both occluded and was occluded by heterosynaptically induced LTD. Inhibition of either protein kinases C or G prevented induction of both forms of LTD.
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PMID:cGMP acts within cerebellar Purkinje cells to produce long term depression via mechanisms involving PKC and PKG. 751 98

1. The purpose of this study was to examine whether depolarizations evoked by excitatory amino acids can be recorded quantitatively, in vivo, with a microelectrode incorporated within a microdialysis probe. 2. Microdialysis probes incorporating a chlorided silver wire were implanted in the striatum of anaesthetized rats and perfused with artificial cerebrospinal fluid (ACSF). Increasing concentrations of excitatory amino acids were applied for 2 min via the microdialysis probe, and the extracellular direct current (d.c.) potential was recorded between the microdialysis electrode and a reference electrode placed under the scalp. 3. N-methyl-D-aspartate (NMDA, 25-500 microM), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA, 5-1000 microM), kainate (5-500 microM), and glutamate (0.25-100 mM) evoked concentration-dependent depolarizations with maxima ranging from 7 to 10 mV, i.e. 3 to 10 times larger than those recorded from brain slices in vitro. Depolarizations evoked by glutamate receptor agonists applied by microdialysis shared several features with those recorded from brain slices. The most characteristic were: steep onset and recovery of NMDA and glutamate responses; marked post-depolarization hyperpolarization with NMDA; and very slow recovery after kainate application. At high concentrations (500 microM), NMDA occasionally initiated spreading depression. The relative potency of glutamate and NMDA was of the same order of magnitude to that obtained with the cortical wedge and hippocampal slices, glutamate being 100 to 400 times less potent than NMDA. 4. Two consecutive series of NMDA-stimuli within the same procedure evoked comparable depolarizations, indicating that reliable quantitative analysis of drug action can be performed, with each animal serving as its own control. This is relevant to the study of drugs acting on glutamate receptors especially antagonists. The remarkable inter-animal reproducibility is also a valuable feature.5. Pretreatment with dizocilpine maleate (MK-801, 2mgkg'1, i.p.) reduced by 65% the responses evoked by NMDA (500 fM). The non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX,100 1M) applied via the microdialysis probe reduced by around 78% the responses to AMPA and kainate (250 micro M). The fact that drugs, especially antagonists, can be administered either systemically, or directly through the dialysis probe to by-pass the blood-brain barrier or avoid peripheral effects, is especially relevant for neuropharmacological studies.6. Intracerebral microdialysis combined with in vivo recording of extracellular field potential is a novel and valuable method for the quantitative analysis of the action of drugs acting on glutamate receptors.This method should prove especially useful for comparing the sensitivity of specific brain structures to selective glutamate receptor agonists under normal conditions and when the neuronal micro environment is altered. It should also be useful for investigating the action of other depolarizing agents, such as veratridine, and their antagonists.
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PMID:Intracerebral microdialysis combined with recording of extracellular field potential: a novel method for investigation of depolarizing drugs in vivo. 753 84

The morphologic and histochemical effects of 3-nitropropionic acid (NPA) were examined in cultured murine embryonal carcinoma cells. NPA caused a dose-dependent inhibition of cell proliferation of cultured murine embryonal carcinoma cells at concentrations above 1.05 mM and was lethal at 4.2 mM. Morphologic changes included gross swelling of the cells, swelling of mitochondria and accumulation of organellar debris within the cytoplasm. NPA inhibited the activity of succinate dehydrogenase but not of malate, isocitrate or glucose-6-phosphate dehydrogenases, resulting in a decrease in intracellular ATP. Although succinate dehydrogenase activity was decreased by NPA, propionic acid and its mercapto-, 2-chloro-, and 3-chloro- derivates did not affect enzyme activity. 3-Nitropropanol also inhibited succinate dehydrogenase but only at a much higher concentration than was required with NPA. The results provide evidence that cytotoxicity caused by NPA results from inhibition of succinate dehydrogenase activity leading to depression of ATP synthesis. Loss of cellular integrity is probably a direct consequence of failure of energy-dependent cell homeostatic mechanisms such as the plasma membrane Na+/K+ pump, resulting in swelling and ultimately lysis of the cell.
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PMID:3-Nitropropionic acid toxicity in cultured murine embryonal carcinoma cells. 770 53

1. We have examined plasticity at glutamatergic synapses on neurons in slices of neostriatum, a forebrain area involved in movement and cognitive function. 2. High-frequency stimulation of afferent inputs to neostriatal neurons induced depression of glutamatergic synaptic transmission. Depression could be induced using either prolonged trains or short repetitive bursts of high-frequency stimulation. Depression developed within seconds after such stimulation. Responses recovered to baseline levels within 10 min in most slices but persisted for up to 60 min in others. 3. Postsynaptic passive electrical properties and the ability to elicit action potentials by postsynaptic depolarization were not altered during depression. 4. The magnitude and time course of depression was similar whether postsynaptic responses were mediated by alpha amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or N-methyl-D-aspartate (NMDA) type glutamate receptors. Depression was not altered by antagonism of AMPA or NMDA receptors or potentiation of AMPA receptor function with aniracetam. 5. Depression was blocked by treatments that increase transmitter release including increased extracellular Ca2+, application of 4-aminopyridine, or application of phorbol ester. 6. Our findings indicate that glutamatergic synapses in neostriatum are capable of expressing a form of synaptic depression that may involve decreased glutamate release.
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PMID:Short- and long-term synaptic depression in rat neostriatum. 790 31

1. The presynaptic depressant action of L-2-amino-4-phosphonobutyrate (L-AP4) on the monosynaptic excitation of neonatal rat motoneurones has been differentiated from the similar effects produced by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate ((1S,3R)-ACPD), (1S,3S)-ACPD and (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine (L-CCG-I), and from the postsynaptic motoneuronal depolarization produced by (1S,3R)-ACPD, by the actions of two new antagonists, alpha-methyl-L-AP4 (MAP4) and alpha-methyl-L-CCG-I (MCCG). Such selectivity was not seen with a previously reported antagonist, (+)-alpha-methyl-4-carboxyphenylglycine (MCPG). 2. MAP4 selectively and competitively antagonized the depression of monosynaptic excitation produced by L-AP4 (KD 22 microM). At ten fold higher concentrations, MAP4 also antagonized synaptic depression produced by L-CCG-I but in an apparently non-competitive manner. MAP4 was virtually without effect on depression produced by (1S,3R)- or (1S,3S)-ACPD. 3. MCCG differentially antagonized the presynaptic depression produced by the range of agonists used. This antagonist had minimal effect on L-AP4-induced depression. The antagonism of the synaptic depression effected by (1S,3S)-ACPD and L-CCG-I was apparently competitive in each case but of varying effectiveness, with apparent KD values for the interaction between MCCG and the receptors activated by the two depressants calculated as 103 and 259 microM, respectively. MCCG also antagonized the presynaptic depression produced by (1S,3R)-ACPD. 4. Neither MAP4 nor MCCG (200-500 microM) significantly affected motoneuronal depolarizations produced by (1S,3R)-ACPD. At the same concentrations the two antagonists produced only very weak and variable effects (slight antagonism or potentiation) on depolarizations produced by (S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA).5. It is concluded that MAP4 is a potent and selective antagonist for those excitatory amino acid(EAA) receptors on neonatal rat primary afferent terminals that are preferentially activated by L-AP4,and that MCCG is a relatively selective antagonist for different presynaptic EAA receptors that are preferentially activated by (1S,3S)-ACPD and (perhaps less selectively) by L-CCG-I. These receptors probably comprise two sub-types of metabotropic glutamate receptors negatively linked to adenylyl cyclase activity.
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PMID:Actions of two new antagonists showing selectivity for different sub-types of metabotropic glutamate receptor in the neonatal rat spinal cord. 792 6

The effects of transgalactosylated disaccharide (TD) intake on human fecal microflora and their metabolism were investigated in 12 Japanese males. TD is a mixture of sugars, galactosyl galactose, and galactosyl glucose, synthesized from lactose through the transgalactosylation reaction of Streptococcus thermophilus beta-galactosidase. Volunteers took 15 g of the test sugar daily for 6 days. The TD ingestion increased the number of bifidobacteria and lactobacilli, but decreased the number of Bacteroidaceae and Candida spp. in the feces. The ratio of bifidobacteria to total bacteria increased from 0.28 to 0.51. TD decreased the fecal concentrations of propionic acid, isobutyric acid, isovaleric acid, and valeric acid. This sugar also lowered the fecal pH, and the concentrations of fecal ammonia, p-cresol, and indole. Moreover, a positive correlation was found between the concentration of ammonia, and that of branched-chain fatty acids (isobutyric acid and isovaleric acid), p-cresol, and indole. All of these compounds are produced from amino acids through deamination by the intestinal bacteria. The depression of amino acid fermentation by intestinal bacteria may be involved in the reduction of fecal ammonia. These results suggest that a part of the transgalactosylated disaccharides passes into the colon, inducing changes in the colonic microflora composition, hastening carbohydrate fermentation, and depressing amino acid fermentation in the human gut.
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PMID:Effects of transgalactosylated disaccharides on the human intestinal microflora and their metabolism. 822 19

Stimulation of carotid body chemoreceptors by saline saturated with 100% CO2 elicited an increase in mean arterial pressure, respiratory rate, tidal volume, and minute ventilation (VE). Microinjections of L-glutamate into a midline area 0.5-0.75 mm caudal and 0.3-0.5 mm deep with respect to the calamus scriptorius increased VE. Histological examination showed that the site was located in the commissural nucleus of the nucleus tractus solitarii (NTS). The presence of excitatory amino acid receptors [N-methyl-D-aspartic acid (NMDA); kainate, quisqualate/alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and trans 1-amino-cyclopentane-trans-1,3-dicarboxylic acid (ACPD)] in this area was demonstrated by microinjections of appropriate agonists. Simultaneous blockade of NMDA and non-NMDA receptors by combined injections of DL-2-aminophosphonoheptanoate (AP-7; 1 nmol) and 6,7-dinitro-quinoxaline-2,3-dione (DNQX; 1 nmol) abolished the responses to stimulation of carotid body on either side. Combined injections of AP-7 and DNQX did not produce a nonspecific depression of neurons because the responses to another agonist, carbachol, remained unaltered. Inhibition of the neurons in the aforementioned area with microinjections of muscimol (which hyperpolarizes neuronal cell bodies but not fibers of passage) also abolished the responses to subsequent carotid body stimulation on either side.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Excitatory amino acid receptors in commissural nucleus of the NTS mediate carotid chemoreceptor responses. 838 18

The distribution of glutamate receptors in the cerebellar cortex of the rhesus macaque was examined by light microscopic immunocytochemistry using an antibody specific to the N-methyl-D-aspartate (NMDA) R1 receptor subunit (i.e. NMDAR1) as well as antibodies specific to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits (i.e. GluR1, GluR2/3, and GluR4). NMDAR1 immunolabeling was most prevalent in the Purkinje cell perikarya and dendrities, but was also significant in the stellate and basket cells of the granular layer and Golgi cells of the molecular layer. On the other hand, GluRl and GluR4 immunolabeling was concentrated principally in the processes of the Bergmann glia located in the vicinity of the Purkinje cell perikarya. Although GluR2/3 immunolabeling also occurred in these Bergmann glia processes as well as in the Bergmann fibers, it was more pronounced in the Purkinje cell perikarya and dendrites; additionally, significant GluR2/3 labeling was evident in the stellate and basket cells of the molecular layer and medium-size soma of the granular layer (most likely Golgi cells). In situ hybridization histochemistry (ISHH), using cRNA probes to NMDAR1. GluR1.GluR2, and GluR3, showed glutamate receptor mRNA distribution patterns consistent with those disclosed in the immunocytochemical study. Furthermore, the ISHH findings suggest that the positive immunocytochemical labeling of Purkinje cells with the GluR2/3 antibody is most likely due to the gene expression of both GluR2 and GluR3 AMPA receptor subtypes. Taken together, the results are potentially important for the elucidation of mechanisms that control aspects of cerebellar function, such as long-term depression.
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PMID:Distribution of NMDA and AMPA receptors in the cerebellar cortex of rhesus macaques. 873 16

We have previously shown that brief high frequency stimulation of the anteromedial prefrontal cortex induces a long-term decrease in excitability of the glutamatergic corticostriatal terminal field. In contrast, a long-term increase in presynaptic corticostriatal excitability may be induced by presenting two brief cortical tetanizing stimuli separated by 2-3 min such that the second tetanus coincides with a period of increased excitability elicited by the first. In the present study, we examined the glutamate receptor subtypes involved in these long-term changes in presynaptic excitability. A specific glutamate receptor antagonist was infused into the rat striatum 10-25 min prior to either a single or double cortical tetanic stimulation. To eliminate the participation of intrinsic striatal cells, a subset of animals received a striatal kainic acid lesion eight to 20 days before the recording experiment. Antagonists of the N-methyl-D-aspartate and metabotropic glutamate receptor subtypes were effective in blocking the decrease in excitability induced by single cortical tetanic stimulation whereas an antagonist of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate receptor did not prevent the induction of a long-term reduction in excitability. In contrast, each of these antagonists prevented the induction of a long-term increase in excitability. These long-term modifications in excitability of the presynaptic glutamate axon terminals appear to be induced by similar mechanisms to those postulated to operate in long-term potentiation and depression. These enduring changes in presynaptic excitability are likely to represent important mechanisms for the selective modification of information processing in the striatum.
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PMID:Glutamate-dependent long-term presynaptic changes in corticostriatal excitability. 878 35


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