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Biomedical subjects

S Kito

Publications and source records attributed to S Kito.

At least 55 records · Page 3Linked to original sources

Influence of age on N-methyl-D-aspartate antagonist binding sites in the rat brain studied by in vitro autoradiography.

The N-methyl-D-aspartate (NMDA) receptor complex has been considered to consist of an L-glutamate recognition site, a strychnine-insensitive glycine modulatory site, and a voltage-dependent cation channel. In this study, an effect of age on NMDA antagonist binding sites was investigated through quantitative in vitro autoradiography with 3H-3-((+)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). 3H-CPP binding sites were most concentrated in the hippocampus and cerebral cortex where NMDA receptors have been demonstrated to be involved in synaptic transmission. In aged rats, 3H-CPP binding sites in the hippocampus and cerebral cortex were not significantly changed. As for other brain regions, there was an age-dependent decline of binding sites only in the caudate-putamen and nucleus accumbens. Our previous study revealed that strychnine-insensitive glycine receptors were markedly reduced in telencephalic regions in the aged rat brain. Taking these findings into consideration, it is concluded that glycine receptors but not NMDA antagonist binding sites are severely altered in telencephalic regions of aged animals. It is considered that within the NMDA receptor complex, glycine receptors may be selectively affected in the aging process.

Aging↗

Effect of age on alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) binding sites in the rat brain studied by in vitro autoradiography.

Receptors for excitatory amino acid, L-glutamate, have been classified into three subtypes named as N-methyl-D-aspartate (NMDA), quisqualate (QA) and kainate receptors. In the present study, an effect of age on binding sites of [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (3H-AMPA), a QA agonist, was studied in the rat brain through quantitative in vitro autoradiography. 3H-AMPA binding sites were most concentrated in the hippocampus and cerebral cortex where glutamate receptors have been demonstrated to play a role in synaptic transmission. In aged rats, 3H-AMPA binding sites in the hippocampus and cerebral cortex were not significantly changed. In our previous studies, it was noticed that strychnine-insensitive glycine receptors, which functionally coupled with NMDA receptors, showed marked age-dependent decreases in telencephalic regions. It has been shown that the glutamatergic neuronal system is involved in learning and memory. Nevertheless, it is considered that AMPA binding sites are not involved in the decline of neuronal functions, especially impairment of learning and memory, accompanying with aging process.

Aging↗

Cholecystokinin increases intracellular Ca2+ concentration in cultured striatal neurons.

Although it has been established that pancreatic cholecystokinin (CCK) receptors are coupled to phosphatidylinositol turnover, the events which follow activation of CCK receptors in the central nervous system have not received much attention. In this paper, changes in intracellular Ca2+ concentration ([Ca2+]1) in response to CCK peptides were measured in single cultured rat striatal neuron by fura-2 fluorometry. CCK peptides dose-dependently increased [Ca2+]i in a monophasic manner. The order of the potencies of CCK peptides to increase [Ca2+]i was as follows: caerulein greater than CCK-8 greater than desulfated CCK-8 greater than CCK-4. The effect of caerulein was completely blocked in a Ca2(+)-depleted medium. In addition, omega-conotoxin GVIA completely inhibited the effect of caerulein, while neither nifedipine nor verapamil affected it. Our results indicate that CCK receptors couple to N-type voltage-sensitive Ca2+ channels in cultured rats striatal neurons.

Animals↗

The effect of bovine brain gangliosides on essential tremor.

We reported the case of a 74-year-old woman suffering from essential tremor for 20 years which was treated effectively with purified bovine brain gangliosides containing GM1, GD1a, GD1b and GT1b gangliosides. The trials of the treatment were conducted twice, 40 mg and 20 mg gangliosides per day respectively administered intramuscularly. Essential tremor dramatically improved with gangliosides on the second day of treatment, suggesting that the effect of gangliosides was not induced by neuronal sprouting or regeneration. It is speculated that a certain type of essential tremor is a reversible disease of membrane disorder.

Aged↗

Age-related changes of strychnine-insensitive glycine receptors in rat brain as studied by in vitro autoradiography.

Age-related changes of strychnine-insensitive glycine receptors in the rat brain were studied through quantitative in vitro autoradiography with 3H-glycine. 3H-glycine binding sites were most concentrated in the hippocampus, cerebral cortex, and olfactory tubercle, and moderate densities of binding sites were located in the striatum, nucleus accumbens, amygdala, and certain thalamic nuclei. Low densities of 3H-glycine binding sites were observed in the lateral septal nucleus, midbrain nuclei such as the superior colliculus and central gray matter, and granule cell layer of the cerebellum. In aged animals, severe decline of 3H-glycine binding sites was observed in the telencephalic regions including the hippocampus and cerebral cortex. On the other hand, decrease of binding sites in the midbrain nuclei was of lesser degree, and there were no changes in the cerebellum. These results suggest that the decrease of glycine receptors in particular brain regions has some relation with changes of neuronal functions associated with aging process in these areas. The glutamatergic neuronal system, particularly the N-methyl-D-aspartate (NMDA) subtype, has been considered to play an important role in learning and memory. Taking into consideration that strychnine-insensitive glycine receptors are contained in the NMDA receptor complex, the present study implies that the decrease of glycine receptors may be involved in impairments of learning and memory occurring in aged brains.

Aging↗

Ontogeny of phorbol ester receptors in rat brain studied by in vitro autoradiography.

The ontogeny of phorbol ester receptors, which have been considered to correspond to protein kinase C, in the rat brain was studied through in vitro autoradiography with 3H-phorbol 12,13-dibutyrate (3H-PDBu). The distribution of 3H-PDBu binding sites in the adult rat brain was similar to the previous reports by other researchers. The developmental pattern of 3H-PDBu binding sites varied with brain region. 3H-PDBu binding sites in the amygdala, thalamus, stratum pyramidale of CA 1 of the hippocampus, dentate gyrus, superior colliculus, substantia nigra, interpeduncular nucleus and cerebellar molecular layer were postnatally increased to adult levels and after that they remained constant. On the other hand, in the stratum oriens and stratum radiatum of CA 1 of the hippocampus, and in the lateral and medial geniculate bodies, 3H-PDBu binding sites reached peaks at 21 or 28 days of postnatal age and after that they declined to adult levels. The cerebellar granular layer showed a low level of 3H-PDBu binding sites throughout all the ontogenetic stages. A distinct ontogenetic pattern of phorbol ester receptors in various regions of the brain may reflect a role of protein kinase C in the neural development of each discrete area.

Animals↗

Mapping of somatostatin receptor localization in rat brain: forebrain and diencephalon.

Using quantitative in vitro receptor autoradiography, minute distributions of 125I-Tyr11-somatostatin (SS)-14 binding sites were investigated in the rat forebrain and diencephalon. In the cerebral cortex, there was a high density of receptors observed in layers V-VI and a low density in layers I-IV. The entorhinal cortex displayed the highest receptor density of the cerebral cortices. The olfactory system had a high SS receptor density. The anterior olfactory nucleus, nucleus of the lateral olfactory tract, medial habenular nucleus and the basolateral amygdaloid nucleus showed moderate densities. In the limbic system, the CA1 and subiculum regions had high receptor densities. More detailed observations revealed high receptor densities in the oriens, radiatum and lacunosum layers and a much lower density in the pyramidal cell layer. The caudate putamen and substantia nigra showed low receptor densities, while the claustrum displayed the highest density of receptors in the rat brain. These data were not consistent with those of previous studies using 125I-SS-28 and 125I-201-995, which had shown that the high receptor density area in the basolateral amygdaloid group was identified as the lateral amygdaloid nucleus, and that the pyramidal cell layer in the hippocampus showed high receptor densities.

Animals↗

Influence of age on NMDA receptor complex in rat brain studied by in vitro autoradiography.

N-methyl-D-aspartate (NMDA) receptors are known to play an important role in learning and memory and to be involved in neuron cell death accompanying cerebral ischemia, seizures, and Alzheimer's disease. The NMDA receptor complex has been considered to consist of an L-glutamate recognition site, a strychnine-insensitive glycine modulatory site, and a voltage-dependent cation channel. In the present study, effects of age on an L-glutamate recognition site and a glycine site were examined in rat brain by quantitative in vitro autoradiography with [3H]-CPP and [3H]-glycine. Both [3H]-glycine and [3H]-CPP binding sites were most abundant in the hippocampus and cerebral cortex, and they showed a similar distribution pattern throughout the brain. [3H]-glycine binding sites were severely decreased in the telencephalic regions, including the hippocampus and cerebral cortex, in aged brain. Conversely, [3H]-CPP binding sites were well preserved in these brain areas. In the mid-brain regions and cerebellum, neither [3H]-glycine nor [3H]-CPP binding sites changed in the aged brain. Our results indicate that within the NMDA receptor complex, glycine receptors are primarily affected in the aging process.

Aging↗

Alteration of muscarinic receptor subtypes in CA1 field of hippocampus in senile dementia of Alzheimer type: an autoradiographic study.

This investigation confirmed decreases in muscarinic acetylcholine receptor (mAChR) concentration in the hippocampus of patients with senile dementia of Alzheimer-type (SDAT) using a binding assay with homogenate. We performed quantitative in vitro autoradiography of mAChR in the hippocampus obtained at autopsy from non-demented controls and SDAT patients, who had a marked memory disturbance since the early stage. 3H-QNB (1.09nM) and 3H-pirenzepine (18.0nM) were used as ligands to label total mAChR and M1 receptors, respectively. Total mAChR and M1 receptor densities showed a decrease by about 20% and 25%, respectively, in the CA1 area of SDAT cases, when compared with that of normal control cases. No changes were observed in the dentate gyrus, CA3, subiculum or entorhinal cortex. These observations are thought to be partly causative of the marked memory deficits which appeared in these cases.

Adult↗

[Guillain-Barré syndrome and disturbance in multiple organs associated with cytomegalovirus infection].

We presented a case of Guillain-Barré syndrome (GBS) associated with pneumonitis, liver, pancreatic and renal dysfunction, and encephalopathy, who showed an increase in anti-cytomegalovirus (CMV) antibody titer of the serum and cerebrospinal fluid (CSF). A 41-year-old male admitted to our hospital with complaints of gait disturbance and muscle weakness in the extremities. The symptoms appeared following common cold, and developed gradually. Neurological examination showed mild mental symptoms, bilateral abducens, facial and bulbar palsy. Muscle weakness was shown on the neck and four extremities. Bilateral hand tremor, glove and stocking type sensory disturbance, and dysautonomia were also presented. Examination of the CSF revealed albumin-cytologic dissociation, and the anti-CMV antibody titer of the serum and CSF increased significantly. The titer of anti-CMV IgG antibody was 1:6400 in the serum, and was 1:80 in the CSF. Immunological examination showed no immunodeficiency. The conduction velocity of the peripheral motor and sensory nerves was decreased. The coefficient variation (CV%) of the R-R interval was also decreased. P1 and P2 latency and central conduction time for a somatosensory evoked potential (SEP) were also elongated, and paroxysmal abnormality was present on electroencephalogram (EEG). Two days after admission, pneumonitis appeared, leading to respiratory insufficiency. He needed respirator because of bulbar and respiratory disturbance. The chest roentgenogram revealed a consolidation-like shadow in the right upper lung filed. Two weeks after admission, liver, pancreatic and renal dysfunction was noted by biochemical examination of the blood, urinalysis, and abdominal echography. Since 10 days after the onset of GBS, 70 mg/day prednisolone was administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of anticholinergic antiparkinsonian drugs on binding of muscarinic receptor subtypes in rat brain.

Anticholinergic antiparkinsonian drugs have been widely used for the treatment of extrapyramidal disorders for a long time although their pharmacological characterization has been unclear. We studied the rank of potency of the effects of anticholinergic antiparkinsonian drugs to binding of 3H-QNB and 3H-PZ and calculated the affinity of each drug to the M1 receptor. All the drugs were potent inhibitors of 3H-QNB and 3H-PZ binding. The order of potency for 3H-QNB being: mazaticol greater than atropine greater than piroheptine greater than trihexyphenidyl greater than biperiden greater than ethopropazine greater than pirenzepine. The order of potency for 3H-PZ being: mazaticol greater than atropine greater than trihexyphenidyl greater than biperiden greater than ethopropazine greater than pirenzepine. Ki ratio indicated that trihexiphenidyl and biperiden bound to the M1 receptors selectively with high affinity and mazaticol would bind to the M2 receptors with higher affinity than atropine. These data suggest that we may be able to consider the pathophysiology of some extrapyramidal disorders based on the therapeutic efficacy of anticholinergic drugs which selectively affect M1 or M2 receptors.

Animals↗

Increase of muscarinic receptor following kainic acid lesions of the nucleus basalis magnocellularis in rat brain: an autoradiographic study.

We observed changes in cholinergic markers in rat brain seven days after lesioning the nucleus basalis magnocellularis (nbm) with kainic acid. In histochemical preparations stained for acetylcholinesterase (AChE), there was a marked loss of large AChE reactive neurons within and beneath the nbm on the injected side, and the AChE positive fibers were greatly decreased particularly in the IV-VI layers of the frontal and parietal cortices ipsilateral to the kainate lesion. Using in vitro receptor autoradiography, we found a significant increase (about 25%) in 3H-QNB binding sites in the I-IV layers of the ipsilateral frontal and parietal cortices (p 0.05, Student's t-test). The area with decreased AChE activity and increased density in 3H-QNB binding sites corresponded to the innervation of the cholinergic system arising from the nbm. The increase of density in 3H-QNB binding sites was considered to reflect the postsynaptic denervation supersensitivity.

Acetylcholinesterase↗

Effect of cerulein on in vivo release of acetylcholine from the rat striatum.

An effect of cerulein on in vivo release of acetylcholine (ACh) from the rat striatum was examined by means of intracerebral dialysis. Intraperitoneal administration of cerulein (25-200 micrograms/kg) enhanced a spontaneous release of ACh in a dose-dependent manner. Intraperitoneal administration of cerulein (100 micrograms/kg) also enhanced the K+-evoked (30 mM) release of ACh. Bilateral subdiaphragmatic vagotomy reduced the increase of both K+-evoked and that of spontaneous release of ACh induced by cerulein administration. Pretreatment with haloperidol (0.5 mg/kg, i.p.) had no effect on increase in spontaneous release of ACh brought about by cerulein administration (100 micrograms/kg, i.p.). These results suggested that peripherally administered cerulein stimulated striatal cholinergic neurons, that its stimulatory effect on striatal ACh release was not mediated by striatal dopamine D2 receptors and that the action of cerulein was, in part, mediated via vagal afferent impulses.

Acetylcholine↗