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E Sakurai

Publications and source records attributed to E Sakurai.

At least 73 records · Page 4Linked to original sources
PubMed1997

Effect of cocaine on the histaminergic neuron system in the rat brain.

To examine the effect of cocaine on the brain histamine neuron system, histamine levels and histamine N-methyltransferase activity in the rat brain were measured after the administration of cocaine. Moreover, we examined the effect of L-histidine on cocaine-induced wheel-running behavior. The administration of cocaine (20 mg/kg) increased histamine levels and histamine N-methyltransferase activity in the striatum, nucleus accumbens, and amygdala 1 h later. The pretreatment with L-histidine (350 and 700 mg/kg) inhibited the cocaine (20 mg/ kg)-induced increase of wheel-running activity in a dose-dependent manner. These findings suggest that cocaine activates the brain histamine neuron system, which may play the role of inhibiting the cocaine-induced wheel-running behavior.

Amygdala↗
PubMed1997

Stereoselective N-demethylation of chlorpheniramine by rat-liver microsomes and the involvement of cytochrome P450 isozymes.

Previous studies have suggested that degradation of the two stereoisomers of chlorpheniramine in the liver might be catalysed by different types of cytochrome P450. Stereoselective N-demethylation of chlorpheniramine and the involvement of cytochrome P450 (CYP) isozymes have, therefore, been investigated in the liver microsomes of eight-week-old male rats. Incubation of racemic chlorpheniramine with liver microsomes from the male rat resulted in the formation of both enantiomers of monodesmethylchlorpheniramine (DMChp). Further metabolism of DMChp to didesmethylchlorpheniramine (DDMChp) did not, however, occur. The S/R enantiomeric ratio for intrinsic clearance (Vmax/Km) was approximately 2.0, suggesting that the N-demethylation was stereoselective for S-(+)-chlorpheniramine. On the other hand, although the Vmax/Km value for the formation of S-(+)- and R-(-)-DMChp increased with phenobarbitone-inducible rat-liver microsomes, there was no difference between the rates of N-demethylation of the enantiomers. In contrast, 3-methylcholanthrene reduced the intrinsic clearance of S-(+)-chlorpheniramine by N-demethylation and increased its value for R-(-)-chlorpheniramine, showing no stereoselectivity for the N-demethylation of chlorpheniramine. The difference between the intrinsic clearance of the two enantiomers by N-demethylation was because of differences in affinity for the catalysing enzyme. This is indicative of stereoselective involvement of the main enzyme concerned in the N-demethylation of the enantiomers, considered to be CYP 2C11. Anti-CYP 2C11 also partially inhibited the N-demethylation of racemic chlorpheniramine in rat-liver microsomes exposed to phenobarbitone and 3-methylcholanthrene. That CYP 2B1 was involved in the N-demethylation of both enantiomers was also supported by results from an experiment using phenobarbitone-inducible rat-liver microsomes. CYP1A1 did not, however, catalyse the N-demethylation of either enantiomer. These results indicate that N-demethylation of the S-(+)-enantiomer of chlorpheniramine occurs preferentially in the microsomes, demonstrating the stereoselective contribution of CYP2C11. Immunoinhibition studies suggest, moreover, that the N-demethylation of both chlorpheniramine enantiomers is catalysed by CYP2B1, but not by CYP1A1.

Animals↗
PubMed1997

The effect of haloperidol on the histaminergic neuron system in the rat brain.

In this study, the effect of haloperidol on histamine (HA) levels, histidine decarboxylase (HDC) activities and the bindings of [3H]-(R)-alpha-methylhistamine ([3H]-(R)-alpha-MeHA) to histamine H3 receptors were investigated in the rat brain. Administration of 10 mg/kg of haloperidol decreased HA levels in the rat striatum and diencephalon, but increased HDC activities in rat striatum and diencephalon, although that of 5 mg/kg did not change them. Meanwhile, haloperidol inhibited the bindings of [3H]-(R)-alpha-MeHA to H3 receptor sites in the rat striatal membrane with a Ki value of 10.5 +/- 0.45 microM. These findings suggest that only a high dose of haloperidol increases HA synthesis and release as a histamine H3 receptor antagonist in the rat brain.

Animals↗
PubMed1996

The effect of methamphetamine on histamine level and histidine decarboxylase activity in the rat brain.

To examine biochemical changes in the brain histamine (HA) neuron system after acute and chronic administrations of methamphetamine (MAP), HA levels and histidine decarboxylase (HDC) activities in the rat cortex, striatum, diencephalon, midbrain, pons-medulla and cerebellum were measured. In the cortex and striatum, acute administration of MAP (1 and 3 mg/kg) increased HA levels 1 h later. Acute administration of MAP (10 mg/kg) and chronic administration of MAP (3 mg/kg) for 21 days also increased HA levels and HDC activities in the cortex and striatum I h after the last injection. In the diencephalon, acute administration of MAP (3 and 10 mg/kg) and chronic administration of MAP (3 mg/kg) decreased HA level 1 h after the last injection, but chronic administration of MAP (3 mg/kg) increased HDC activity 1 h after the last injection. There were no significant changes in HA levels and HDC activities in other regions after acute and chronic administrations of MAP. These findings suggest that MAP may activate the brain HA neuron system, although MAP acts more strongly on the cortex and striatum than on the diencephalon.

Animals↗
PubMed1996

Galanin inhibits long-term potentiation at Schaffer collateral-CA1 synapses in guinea-pig hippocampal slices.

The role of galanin on long-term potentiation (LTP) of the field excitatory postsynaptic potentials (fEPSPs) at Schaffer collateral-CA1 synapses was investigated in guinea-pig hippocampal slices. Application of galanin (10(-7) M) inhibited the magnitude of LTP without any changes in the amplitude of fEPSP prior to tetanic stimulation. A putative central nervous system (CNS) type galanin receptor antagonist, galanin(1-13)-Pro-Pro-(Ala-Leu)2-Ala-Amide (M40), did not modify the magnitude of LTP when applied alone. However, M40 significantly reversed the inhibition by galanin when applied with galanin simultaneously. These findings suggest that galanin plays an inhibitory role through the CNS type galanin receptors.

Animals↗
PubMed1996

In-vivo microdialysis measurement of 5-hydroxytryptamine and its metabolites, 5-hydroxyindoleacetic acid and N-acetyl 5-hydroxytryptamine, in rat blood: effects of histamine-receptor antagonists.

The blood concentrations of 5-hydroxytryptamine (5-HT) and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and N-acetyl 5-HT were assayed by in-vivo microdialysis and a highly sensitive HPLC procedure that was originally developed to analyse CNS mediators. We investigated the effects of histamine-receptor antagonists on 5-HT metabolism and its release into the blood of rats. The mean basal levels of 5-HT, 5-HIAA and N-acetyl 5-HT in the blood measured by in-vivo microdialysis were 77.2 +/- 9.4, 20.3 +/- 1.5 and 1.89 +/- 0.15 pmol mL-1, respectively. These levels were not significantly affected by an intraperitoneal injection of saline, and remained at constant levels for at least 8 h after administration of saline. After an intraperitoneal injection of 5-HT hydrochloride (0.5 mg kg-1), 5-HT was soon detected in the blood of the jugular vein. 5-HIAA also quickly appeared in the blood and declined monoexponentially from 60 min after injection. In contrast, N-acetyl 5-HT slowly appeared in the blood and it reached a maximal level at 270 min. The 5-HT and N-acetyl 5-HT levels in dialysates from rat jugular vein were significantly increased by intraperitoneal pyrilamine (2.0 mg kg-1), (+)-chlorpheniramine (2.0 mg kg-1) and cimetidine (20.0 mg kg-1). However, there was no increase in the 5-HIAA concentration after an intraperitoneal injection of these histamine-receptor antagonists, demonstrating that the 5-HT released from various cells containing 5-HT was predominantly metabolized to N-acetyl 5-HT by N-acetyltransferase. Moreover, thioperamide did not affect the basal levels of 5-HT, 5-HIAA or N-acetyl 5-HT. Because the recovered 5-HT, 5-HIAA and N-acetyl 5-HT in the dialysate is directly proportional to the free fraction in the blood, in-vivo microdialysis is a reliable method of examining 5-HT metabolism and its release into the blood.

Animals↗
PubMed1996

Nitrogen dioxide exposure increases airway contractile response to histamine by decreasing histamine N-methyltransferase activity in guinea pigs.

To determine the mechanism responsible for nitrogen dioxide (NO2)-induced airway hyperresponsiveness, we examined the effects of NO2 exposure on the contractile response to histamine and the level of histamine N-methyltransferase (HMT) activity, a histamine-degrading enzyme, in guinea pig trachea in vitro. Guinea pigs were divided into seven groups. Each group received continuous NO2 exposure (2.0 ppm) for either 2, 6, 12, 24, 48, or 96 h. The remaining group did not receive NO2 exposure (control). HMT activity in trachea was decreased from the control value of 70.3 +/- 7.7 pmol/min/mg protein to 34.6 +/- 6.7 pmol/min/mg protein by 12 h exposures of NO2. However, 24 and 48 h exposures of NO2 did not significantly alter HMT activity. In contrast, HMT activity exceeded the control value by 96 h exposures of NO2 (85.5 +/- 5.1 pmol/min/mg protein). Twelve hour exposures of NO2 shifted the concentration-response curves to histamine to lower concentrations and significantly reduced the median effective concentration (EC50) of histamine (log M) from the control value of -5.16 +/- 0.09 to -6.15 +/- 0.14 (P < 0.01). In contrast, the EC50 concentration of histamine (log M) increased from the control value of -5.20 +/- 0.10 to -4.90 +/- 0.11 by 96 h exposures of NO2 (P < 0.05). However, NO2 exposure did not alter the contractile response to acetylcholine. Morphologically, tracheal epithelial cells had vacuoles after 12 h exposures of NO2, but denudation of the epithelium did not occur during this experiment. In situ hybridization for HMT mRNA demonstrated that the level of HMT mRNA increased dominantly in tracheal epithelial cells after 96 h exposures of NO2. The present results indicated that the decrease in the level of HMT activity in the trachea was closely associated with the increase in the airway contractile response to histamine, suggesting that NO2-induced transient airway hyperresponsiveness to histamine is due to the decreased capacity of histamine catabolism in airway.

Animals↗
PubMed1996

Effects of dopamine antagonists on neuronal histamine release in the striatum of rats subjected to acute and chronic treatments with methamphetamine.

In this study, we examined the changes in neuronal histamine (HA) release in the rat striatum after acute and repeated administration of methamphetamine (METH). We studied the regulation of METH-induced HA release by dopamine receptors and the relationship between METH-induced HA release and stereotyped behavior. Acute administration of METH (1 mg/kg) significantly increased HA release 60 min later. Pretreatments with the dopamine D2 antagonists sulpiride and haloperidol blocked the METH-induced increase of HA release, whereas pretreatment with a dopamine D1 antagonist, SCH23390, did not. Moreover, repeated administration of METH (3 mg/kg) greatly enhanced the METH-induced increase of HA release 60, 80, 100, 120 and 180 min after rechallenge of METH (1 mg/kg). Repeated treatment with haloperidol and METH blocked the increase of HA release induced by the rechallenge of METH. The METH-induced increase of HA release was still found after the METH-induced stereotyped behavior decreased in both acute and repeated administrations of METH. These findings suggest that the METH-induced HA release in the striatum is controlled by dopamine D2 receptors and may play an important inhibitory role in the METH-induced stereotyped behavior. Furthermore, a persistent change in the HA neuron system through DA neurotransmission may be partially responsible for the METH-induced behavioral sensitization.

Animals↗
PubMed1996

[A case of nonrhegmatogenous retinal detachment in Dandy-Walker Syndrome].

A 2-month-old female presented with nonrhegmatogenous retinal detachment in Dandy-Walker syndrome. At the fist examination, coloboma involving the optic disc in both eyes was detected. The left eye showed microphthalmos with sclerocornea, persistent pupillary membrane, hypoplasia of the iris stroma, and bullous retinal detachment near the optic disc. Chromosomal analysis revealed a mosaic pattern: 46, XX/47, XXX. Increased intracranial pressure associated with Dandy-Walker syndrome was detected by a neurosurgeon at the age of 3 months. The patient was followed for several weeks, and then nonrhegmatogenous retinal detachment appeared in the right eye. Subretinal fluid alternately increased and decreased in both eyes. A ventriculo-peritoneal shunt was performed at the age of 6 months, and the retinal detachment was remarkably reduced in both eyes after lowering of intracranial pressure. Coloboma involving the optic disc, sclerocornea, persistent pupillary membrane, hypoplasia of iris stroma, and Dandy-Walker syndrome were thought to be caused by the abnormal development of neural crest cells. We surmised that the retinal detachment in this case might have resulted from a communicating pathway between the subarachnoid space and the subretinal space. We concluded that the etiology of retinal detachment associated with optic disc anomaly should be investigated to determine adequate treatment.

Coloboma↗
PubMed1995

Long-term depletion of brain histamine induced by alpha-fluoromethylhistidine increases feeding-associated locomotor activity in mice with a modulation of brain amino acid levels.

We examined the long-term effects of administration of (S)-alpha-fluoromethylhistidine (FMH), a specific inhibitor of histidine decarboxylase, on the spontaneous locomotor activity, food intake and brain contents of histamine, catecholamines, serotonin and amino acids of ICR mice. The distance of ambulation and number of rearings significantly increased from 8 to 15 h (20.00-03.00 h) after treatment with FMH (100 mg/kg, i.p.) and the 24-h food intake also increased significantly. On FMH treatment, the locomotor activity in movements of 3-15 cm/0.5 s was greater than that of control mice, whereas the number of slight movements (0-1 cm/0.5 s) decreased, suggesting that once a mouse treated with FMH is in motion, it moves a longer distance than a control mouse. We sacrificed mice 12 or 24 h after FMH treatment to measure the brain contents of histamine, monoamines and amino acids. Decrease of the brain histamine content to 35% of the control level was observed until 24 h after FMH treatment, but no significant changes in the brain catecholamine and serotonin contents were detected. However, the brain GABA content of ICR mice decreased to 85% of control 12 h after FMH treatment. Moreover, decrease of the brain GABA content after FMH treatment was greater in mast cell-deficient W/Wv mice, being 70 and 62% of the control level 12 and 24 h after treatment, respectively. The present experiments support the idea that the locomotor activity is affected by the central histaminergic system, directly and/or indirectly.

Amino Acids↗
PubMed1995

Ontogenetic development of histamine receptor subtypes in rat brain demonstrated by quantitative autoradiography.

The postnatal ontogenetic development of the histamine receptor subtypes was studied in rat brain by quantitative receptor autoradiography with highly sensitive imaging plates. H1 receptor binding sites labeled with [3H]pyrilamine were detected on postnatal day 2 (P2) and increased very slowly until P9, and then rapidly reaching the adult levels in the hypothalamus, hippocampus, and amygdala by P16. The densities of H1 receptor binding sites in the cortex, striatum, thalamus, and substantia nigra were relatively low during development. H3 receptor binding sites labeled with [3H](R) alpha-methylhistamine were not detectable until P9. On P9, their density was higher in the substantia nigra than in other regions. Subsequently, H3 receptor binding increased, reaching the adult levels in the substantia nigra on P16 and in the other regions on P23. The histamine concentration was initially very high, but decreased to the adult level by P16. On the contrary, the activity of L-histidine decarboxylase of whole brain tissue was low on P5, and increased markedly from P16 to P23, to the adult level on P30. Administration of (S) alpha-fluoromethylhistidine (FMH), a specific inhibitor of L-histidine decarboxylase (HDC), significantly decreased both the HDC activity and histamine concentration during postnatal development. FMH treatment did not change H1 receptor binding in any brain region, but significantly increased H3 receptors in the substantia nigra and striatum on P23. Unilateral injection of 6-hydroxydopamine into the striatum on P2 resulted in up-regulation of H3 receptor binding sites in the dorsomedial (11%) and dorsolateral (18%) regions of the striatum and substantia nigra (31%) on P23, but no change in the H3 receptor density in the nucleus accumbens or frontal cortex on P11 and P23. These results demonstrate that the developmental patterns of H1 and H3 receptors are heterogeneous and independent of each other. There are marked mismatches of presynaptic and postsynaptic markers of the histaminergic neuron system as in other aminergic systems.

Aging↗
PubMed1995

Effects of thioperamide, a histamine H3 antagonist, on the step-through passive avoidance response and histidine decarboxylase activity in senescence-accelerated mice.

The effect of thioperamide, a histamine H3 receptor antagonist, on learning and memory was studied in the senescence-accelerated mice-prone strain (SAM-P/8) and normal-rate aging strain (SAM-R/1). In a passive avoidance test, SAM-P/8 mice of 12 months showed significant impairment of learning and memory compared with SAM-R/1 mice of the same age. Thioperamide significantly improved the response latency in SAM-P/8 mice when injected intraperitoneally at a dose of 15 mg/kg. The histidine decarboxylase (HDC) activity in the forebrain was significantly lower in SAM-P/8 mice than in SAM-R/1 mice. Thioperamide administration significantly potentiated HDC activity in the forebrain of SAM-P/8 mice as well as improving learning and memory. These results suggest that central histaminergic neurons may be involved in learning and memory impairment of SAM-P/8 mice, although other possibilities are not ruled out.

Aging↗
PubMed1995

Brain histaminergic system in mast cell-deficient (Ws/Ws) rats: histamine content, histidine decarboxylase activity, and effects of (S) alpha-fluoromethylhistidine.

The mast cell-deficient [Ws/Ws (White spotting in the skin)] rat was investigated with regard to the origin of histamine in the brain. No mast cells were detected in the pia mater and the perivascular region of the thalamus of Ws/Ws rats by Alcian Blue staining. The histamine contents and histidine decarboxylase (HDC) activities of various brain regions of Ws/Ws rats were similar to those of +/+ rats except the histamine contents of the cerebral cortex and cerebellum. As the cerebral cortex and cerebellum have meninges that are difficult to remove completely, the histamine contents of these two regions may be different between Ws/Ws and +/+ rats. We assume that the histamine content of whole brain with meninges in Ws/Ws rats is < 60% of that in +/+ rats. So we conclude that approximately half of the histamine content of rat brain is derived from mast cells. Next, the effects of (S) alpha-fluoromethylhistidine (FMH), a specific inhibitor of HDC, on the histamine contents and HDC activities of various regions of the brain were examined in Ws/Ws rats. In the whole brain of Ws/Ws rats, 51 and 37% of the histamine content of the control group remained 2 and 6 h, respectively, after FMH administration (100 mg/kg of body weight). Therefore, we suggest that there might be other histamine pools including histaminergic neurons in rat brain.

Alcian Blue↗
PubMed1995

[Stereoselective N-demethylation of chlorpheniramine in rat liver microsomes: studies on age and sex differences].

We have established a simple method for the chiral stationary-phase liquid chromatographic resolution of racemic chlorpheniramine (Chp) and its two N-demethylated metabolites, monodesmethylchlorpheniramine (DMChp) and didesmethylchlorpheniramine (DDMChp), using an ovomucoid-conjugated column with respective quantitation limits of 5 ng/ml. The assay was used to study the age and sex difference in stereoselective N-demethylation of Chp by rat liver microsomes. The formation rate of each DMChp from racemic Chp was about 2.2 times faster with the S-(+)-enantiomer than the R-(-)-enantiomer in male rats at the age of only 8 weeks, whereas the rate of N-demethylation in male rats was not different between S-(+)- and R-(-)-enantiomers at the age of 3 and 24 weeks. The Vmax/Km value for the formation of S-(+)-DMChp increased with age in male rats, but the value in 8-week-old rats was lower than that in 3-week-old rats in the formation of R-(-)-DMChp. In female rats, on the other hand, the formation rate of DMChp from racemic Chp did not differ between S-(+)- and R-(-)-enantiomers at each age, suggesting a lack of stereoselectivity in the microsomal N-demethylation. Moreover, the Km and Vmax values for N-demethylation of Chp enantiomers were nearly identical between two consecutive ages in female rats. Further metabolism of DMChp to DDMChp was not observed between both enantiomers in male and female liver microsomes at the age of 3, 8 and 24 weeks.

Aging↗