Search PubMed⌕ Search

Biomedical subjects

A Kurumaji

Publications and source records attributed to A Kurumaji.

16 recordsLinked to original sources
PubMed1992

Measurement of glutamate, aspartate and glycine and its potential precursors in human brain using high-performance liquid chromatography by pre-column derivatization with dimethylaminoazobenzene [correction of diethylaminoazobenzene] sulphonyl chloride.

This paper describes a high-performance liquid chromatographic technique, with dimethylaminoazobenzene sulphonyl chloride derivatization, for the measurement of glutamate, aspartate and glycine and its potential precursors in human brain tissue. The derivatization procedure is simple, sensitive and highly reproducible. The derivatized amino acids are stable and can be analysed by reversed-phase chromatography with visible detection at an absorption wavelength of 436 nm. A preliminary application to the determination of the concentrations of several amino acids in several regions of the human brain is described.

Aged↗
PubMed1992

Alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding to human cerebral cortical membranes: minimal changes in postmortem brains of chronic schizophrenics.

The binding of alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA), a selective ligand for the ion channel-linked quisqualate receptor, was evaluated in Triton X-100-treated membranes of human cerebral cortex. The presence of chaotropic ions produced divergent effects on specific [3H]AMPA binding: A twofold increase in the binding was observed with thiocyanide at 100 mM, although iodide (100 mM) and perchlorate (100 mM) reduced the binding. Chemical modifications of the sulfhydryl group with p-chloromercuriphenylsulfonic acid (PCMBS) produced threefold increases in specific [3H]-AMPA binding in the absence of KSCN as well as in the presence of KSCN. Treatment with dithiothreitol restored the enhanced specific [3H]AMPA binding by PCMBS to the basal level. Although specific [3H]AMPA binding in the absence of KSCN showed a single site (KD = 220 nM, Bmax = 235 fmol/mg of protein), curvilinear Scatchard plots of specific [3H]AMPA binding in the presence of 100 mM KSCN can be resolved into two binding sites with the following parameters: KD1 = 5.82 nM, Bmax1 = 247 fmol/mg of protein; KD2 = 214 nM, Bmax2 = 424 fmol/mg of protein. Quisqualate and AMPA were the most potent inhibitors of the [3H]AMPA binding in the presence of KSCN. Potent inhibitors of the binding included beta-N-oxalylamino-L-alanine (L-BOAA), cysteine-S-sulfate, L-glutamate, 6-cyano-7-nitroquinoxaline-2,3-dione, and 6,7-dinitroquinoxaline-2,3-dione. Kainate, L-homocysteine sulfinic acid, and L-homocysteic acid were active with an IC50 value of a micromolar concentration, whereas L-cysteic acid and L-cysteine sulfinic acid were weakly active.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Chloromercuribenzenesulfonate↗
PubMed1991

Effects of chronic administration of MK-801 upon local cerebral glucose utilisation and ligand binding to the NMDA receptor complex.

Although clinical use of N-methyl-D-aspartate (NMDA) receptor antagonists will involve prolonged drug administration, knowledge of the functional consequences of chronic NMDA receptor blockade is limited. Local cerebral glucose utilisation was measured in conscious rats in 74 discrete brain regions after chronic administration of (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine (MK-801) (0.5 mg/kg i.p.). Chronic treatment with MK-801 caused small, significant changes in glucose use in 4 of the 74 brain areas; parietal cortex (-13%), frontal cortex (-10%), subthalamic nucleus (-14%) and nucleus accumbens (-17%). These focal alterations in glucose use were not associated with changes in ligand binding to various sites within the NMDA receptor complex (i.e. agonist recognition site, glycine site, ion channel site) which were assessed autoradiographically. The acute effects of MK-801 on glucose utilisation were significantly enhanced after chronic MK-801 in 7 brain regions (e.g. frontal and parietal cortices) and attenuated in 6 brain regions (e.g. nucleus accumbens, hippocampus, posterior cingulate cortex). Neither local enhancement nor attenuation of the acute response to MK-801 was due to alterations in ligand binding to sites within the NMDA receptor complex. The data clearly indicate that the functional consequences of NMDA blockade are altered after chronic MK-801 treatment in an anatomically organised, though complex manner. These adaptive functional changes after chronic MK-801 treatment cannot be attributed readily to alterations in the NMDA receptor complex in affected regions.

Animals↗
PubMed1990

Effects of MK-801 upon local cerebral glucose utilisation in conscious rats following unilateral lesion of caudal entorhinal cortex.

Local cerebral glucose utilisation was examined in 62 discrete regions of conscious rats following unilateral ibotenic acid lesion of the caudal entorhinal cortex, and subsequent pharmacological challenge with (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. Fourteen days after unilateral lesion of the entorhinal cortex, there were no significant alterations in local cerebral glucose use except within the lesioned entorhinal cortex (reduced by 31% compared to sham-operated control animals). In sham-operated animals, systemic administration of MK-801 (0.5 mg/kg, i.v.) induced anatomically organised alterations in glucose use with increases in olfactory areas, subicular complex and some limbic areas (posterior cingulate cortex, mammillary body and anteroventral thalamic nucleus), and decreases in the inferior colliculus and neocortex (auditory, sensory-motor, somatosensory and frontal cortices). In animals with unilateral entorhinal cortex lesions, the metabolic response to MK-801 differed significantly from the response to the drug in sham-lesioned animals in a number of regions, viz. hippocampus, molecular layer (ipsilateral to lesion), entorhinal cortex (ipsilateral), dentate gyrus (ipsilateral), presubiculum (bilateral), parasubiculum (bilateral) and nucleus accumbens (bilateral). The ability of MK-801 to reduce glucose use in the neocortex was not altered by entorhinal cortex lesion. These data suggest that the functional consequences of non-competitive NMDA receptor blockade are dependent in some areas upon the integrity of the perforant pathway from the entorhinal cortex to the hippocampus.

Animals↗
PubMed1990

Effects of unilateral intrahippocampal injection of MK-801 upon local cerebral glucose utilisation in conscious rats.

The effects of unilateral intrahippocampal injections of the non-competitive NMDA receptor antagonist, MK-801, on local cerebral glucose utilisation have been examined in conscious rats using [14C]2-deoxyglucose autoradiography. The intrahippocampal injection of MK-801 (10 nmol) induced significant marked increases in glucose use in the ipsilateral hippocampus molecular layer and dentate gyrus (by 31 and 44%, respectively). Function-related glucose use in brain regions with known neuronal connections with the site of drug administration (e.g. entorhinal cortex, septal nucleus, mamillary body) was minimally altered after intrahippocampal MK-801 administration. Blockade of hippocampal NMDA receptors does not appear to modify activity, as reflected in local glucose utilisation, in hippocampal afferent and efferent circuits in conscious rats.

Animals↗
PubMed1989

Effects of NMDA antagonists, MK-801 and CPP, upon local cerebral glucose use.

The effects upon cerebral glucose utilisation of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801, a non-competitive N-methyl-D-aspartate (NMDA, receptor antagonist) and 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, a competitive NMDA receptor antagonist) were examined in conscious, lightly restrained rats. Cerebral glucose utilisation was assessed quantitatively in 74 brain regions with [14C]2-deoxyglucose autoradiography. The intravenous (i.v.) administration of MK-801 (0.05-5 mg/kg) induced heterogeneous patterns of altered cerebral glucose utilisation with statistically significant increases being observed in 21 brain areas and statistically significant decrease in 8 brain regions. Pronounced dose-related increases in glucose use were observed after MK-801 in the subicular complex, hippocampus molecular layer, dentate gyrus, limbic system (posterior cingulate cortex; mamillary body; anteroventral thalamic nucleus), olfactory areas and substantia nigra (pars reticulata). Glucose use in the neocortex and inferior colliculus was particularly sensitive to reduction by MK-801 administration. The pattern of altered glucose use after administration of CPP (3-30 mg/kg, i.v.) differed markedly from that observed after MK-801 treatment. Statistically significant increases in glucose use after CPP were noted in 11 brain areas and statistically significant decreases in 5 of the regions examined. Regions in which increases were noted after CPP included hippocampus molecular layer, olfactory areas, cochlear nucleus, vestibular nucleus, cerebellar nucleus, superior olives and substantia nigra (pars reticulata). These data indicate that widespread, anatomically organised alterations in cerebral function are associated with the administration of NMDA receptor antagonists despite the minor role normally ascribed to these receptors in conventional fast synaptic transmission. The distinct patterns of response to competitive and non-competitive antagonists may be a reflection of the differential responses of the two modes of receptor blockade to increased glutaminergic transmission.

Animals↗
PubMed1989

Effects of MK-801 upon local cerebral glucose utilisation in conscious rats and in rats anaesthetised with halothane.

The effects of MK-801 (0.5 mg/kg i.v.), a non-competitive N-methyl-D-aspartate (NMDA) antagonist, upon local cerebral glucose utilisation were examined in conscious, lightly restrained rats and in rats anaesthetised with halothane in nitrous oxide by means of the quantitative autoradiographic [14C]-2-deoxyglucose technique. In the conscious rats, MK-801 produced a heterogenous pattern of altered cerebral glucose utilisation with significant increases being observed in 12 of the 28 regions of gray matter examined and significant decreases in 6 of the 28 regions. Pronounced increases in glucose use were observed after MK-801 in the olfactory areas and in a number of brain areas in the limbic system (e.g., hippocampus molecular layer, dentate gyrus, subicular complex, posterior cingulate cortex, and mammillary body). In the cerebral cortices, large reductions in glucose use were observed after administration of MK-801, whereas in the extrapyramidal and sensory-motor areas, glucose use remained unchanged after MK-801 administration in conscious rats. In the halothane-anaesthetised rats, the pattern of altered glucose use after MK-801 differed qualitatively and quantitatively from that observed in conscious rats. In anaesthetised rats, significant reductions in glucose use were noted after MK-801 in 10 of the 28 regions examined, with no area displaying significantly increased glucose use after administration of the drug. In halothane-anaesthetised rats, MK-801 failed to change the rates of glucose use in the olfactory areas, the hippocampus molecular layer, and the dentate gyrus.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1989

Alterations in the N-methyl-D-aspartate receptor complex following focal cerebral ischemia.

The functional integrity of the N-methyl-D-aspartate receptor complex following focal cerebral ischemia in the rat has been examined at a time when brain tissue is irreversibly damaged. Twelve hours after unilateral permanent middle cerebral artery occlusion, [3H]-MK-801 binding was not significantly altered in the ischemic cerebral cortex compared to sham-operated animals. Moreover, the enhancement of [3H]MK-801 binding by exogenous glutamate was preserved in an area of the brain that was permanently damaged by the ischemic insult.

Animals↗
PubMed1988

Differential effects of competitive and non-competitive N-methyl-D-aspartate antagonists on glucose use in the limbic system.

The effects on cerebral glucose utilisation of 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP, a competitive N-methyl-D-aspartate (NMDA) receptor antagonist), and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801, a non-competitive NMDA receptor antagonist) have been examined in conscious rats. Cerebral glucose utilisation was assessed quantitatively with 14C-2-deoxyglucose autoradiography. MK-801 (0.05-5 mg/kg, i.v.) markedly increased glucose use in a number of limbic brain areas such as the mamillary body, anterior thalamic nucleus, posterior cingulate cortex and hippocampus. CPP (3-30 mg/kg, i.v.), in contrast, effected minimal alterations in glucose use in the limbic system. The functional consequences in vivo, as reflected in local cerebral glucose use, of competitive blockade of the NMDA receptor differ markedly from blockade with non-competitive antagonists.

Animals↗
PubMed1988

An increase in striatal Met-enkephalin-like immunoreactivity in neonatally dopamine-depleted rats.

A pronounced decrease in dopamine content in both the striatum and the mesolimbic area was observed up to 120 days of age after treatment with 6-hydroxydopamine (100 micrograms, intracisternally) following desipramine pretreatment (20 mg/kg, i.p.) at the 5th postnatal day. In the 6-hydroxydopamine-treated rats, Met-enkephalin-like immunoreactivity in the striatum was found to have increased at 35 and 70 days old, although it remained unchanged at 25 days old. The neonatal administration of 6-hydroxydopamine, however, did not affect the peptide content in the mesolimbic area at any age. These results indicate that the neonatal dopamine reduction changes the Met-enkephalinergic neuronal activity in the striatum at the adult age.

Age Factors↗
PubMed1988

Chronic dietary treatment with antidepressants decrease brain Met-enkephalin-like immunoreactivity in the rat.

This report describes the effect of chronic dietary treatment with antidepressants or antimanic drugs on brain Met-enkephalin-like immunoreactivity in the rat. The chronic treatment was administered through food containing 250-1000 mg desipramine, imipramine or clomipramine, 200-800 mg amoxapine or mianserin, 750-1500 mg lithium chloride, or 50 mg haloperidol per 1 kg food for 40 days. In the striatum, each antidepressant decreased the enkephalin content, while lithium or haloperidol, having an antimanic effect, increased the enkephalin content. Following the chronic administration of each antidepressant tested, the concentration of the peptide was reduced in the nucleus accumbens, hypothalamus and thalamus. We further examined the acute effect of the antidepressant (10 or 20 mg/kg) on the striatal enkephalin content at 60 min after a single intraperitoneal injection. The striatal content was decreased after the acute treatment with each antidepressant tested. These results indicate that the antidepressants had an effect on the neuronal activity of Met-enkephalin not only after chronic treatment, but also after acute treatment. The reduction in Met-enkephalin-like immunoreactivity after prolonged treatment with the antidepressant may possible contribute to the mechanism of antidepressive action.

Animals↗
PubMed1988

Circadian fluctuations in pain responsiveness and brain Met-enkephalin-like immunoreactivity in the rat.

The 24-hour patterns of pain responsiveness and brain Met-enkephalin-like immunoreactivity (MLI) were determined in male Wistar rats housed under a 12-hour light and dark cycle (lights on from 0700 hr to 1900 hr). A circadian rhythm was observed in latencies to hot plate test (55 degrees C), showing the peak level near the onset of the dark phase (2000 hr). Pretreatment with naloxone (5 mg/kg, subcutaneously) decreased the highest latency (2000 hr), but did not change the lowest latency (1100 hr). In the mesolimbic area and the striatum, MLI had a negative correlation with the circadian fluctuation in pain sensitivity. MLI at 2000 hr was reduced significantly compared to that at 1100 hr in the basal ganglia, the frontal cortex and the substantia nigra. These results suggest that the circadian variation in hot plate latencies follows a circadian change in the activity of the endogenous opioid peptides system, and that Met-enkephalin may participate in the enhancement of the opioid system in the brain.

Animals↗
PubMed1988

Neurotransmitters, receptors and neuropeptides in post-mortem brains of chronic schizophrenic patients.

In the analysis of post-mortem brains of 14 chronic schizophrenic patients and 10 controls, biochemical evidence of a hyperdopaminergic state was found in the basal ganglia of schizophrenics; tyrosine hydroxylase activity was increased with a concomitant increase of homovanillic acid. Unusually high tyrosine hydroxylase activity was noted in 2 schizophrenic cases. The Bmax value of 3H-spiperone binding for schizophrenics was higher than the controls. We also found increased specific binding of 3H-kainic acid to the prefrontal cortex in schizophrenics. A negative correlation existed between 3H-kainic acid binding in the medial frontal cortex, and glutamic acid content in various brain areas. Increased immunoreactivity of substance P was found in more than ten brain areas. Methionine-enkephalin was also increased in three areas of the prefrontal cortex of schizophrenics. These results suggest that the hyperdopaminergic state co-existed with glutamatergic hypofunction and increased neuropeptides in various brain areas of chronic schizophrenic patients.

Adult↗
PubMedDate not supplied

Cold and immobilization stress-induced changes in pain responsiveness and brain Met-enkephalin-like immunoreactivity in the rat.

Pain responsiveness and Met-enkephalin-like immunoreactivity (MLI) were studied in the rat after cold (25 degrees C) and immobilization stress for different lengths of time (30 min, 90 min and 180 min). The 30-min stress-induced analgesia (as measured by the tail-flick method), which was partially antagonized by pretreatment with naloxone (5 mg/kg, SC), and the magnitude of this analgesia was less than that of the 90-min stress or 180-min stress. The 30-min stress resulted in a significant decrease in MLI in the mesolimbic area, striatum, hypothalamus and thalamus. After the 90-min stress, MLI was found to be significantly decreased in the prefrontal cortex, amygdaloid nuclei and piriform cortex, thalamus and hippocampus, while the 180-min stress failed to induce a significant change in any brain area tested. As such a change in MLI content was thought to be related to an increase in the activity of the endogenous Met-enkephalin neuronal system, the activation of this system by the stress, especially in the hypothalamus and thalamus, seemed to be associated with analgesia.

Analgesia↗