Biomedical subjects

K Maeyama

Publications and source records attributed to K Maeyama.

At least 37 records · Page 2Linked to original sources

PubMed1998

Biphasic elevation of plasma histamine induced by water immersion stress, and their sources in rats.

The effect of water immersion stress on the plasma concentration of histamine, in Wistar and mast cell-deficient (Ws/Ws) rats, was investigated. The histamine content of the plasma, skin and gastric mucosa, as well as the level of activity of histidine decarboxylase in the gastric mucosa, were determined by high performance liquid chromatography (HPLC)-fluorometry. In Wistar rats exposed to water immersion stress for a total of 6 h, an initial, acute, four-fold, transient increase in the plasma histamine level, followed by a sustained, though lower, elevation of the plasma histamine level, was observed. The initial acute increase in plasma histamine level was also seen in gastrectomized Wistar rats exposed to water immersion stress, but not in Ws/Ws rats exposed to stress. The sustained elevation of the plasma histamine level was observed in the Ws/Ws rats. However, in both the gastrectomized Wistar rats and gastrectomized Ws/Ws rats, the sustained elevation in plasma histamine level was not observed. The histamine content of the skin of Wistar rats after 15 min or more exposure to water immersion stress, was 20% lower than that of control rats. The mucosal histamine content of both Wistar rats and Ws/Ws rats, was 20% lower, whereas histidine decarboxylase activity in the gastric mucosa was enhanced by two-fold, during exposure to stress for 4 h. These findings indicate that water immersion stress causes a biphasic increase in plasma histamine concentration in Wistar rats; the initial acute increase in plasma histamine level originates from mast cells, and the second, sustained increase is attributed to enterochromaffin-like cells.

Animals↗

PubMed1998

Systematic method to obtain novel genes that are regulated by mi transcription factor: impaired expression of granzyme B and tryptophan hydroxylase in mi/mi cultured mast cells.

The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). We have reported that the expression of several genes was impaired in cultured mast cells (CMCs) of mi/mi genotype, and demonstrated the involvement of MITF in the transcription of these genes. To obtain new genes whose transcription may be regulated by MITF, we prepared a subtracted cDNA library using +/+ and mi/mi CMCs. We found two clones carrying the granzyme (Gr) B and tryptophan hydroxylase (TPH) cDNAs in the subtracted library. The expression of the Gr B and TPH genes decreased in mi/mi CMCs, and recovered to nearly normal level by the overexpression of normal (+) MITF but not of mutant (mi) MITF. The +-MITF bound three and one CANNTG motifs in the Gr B and TPH promoters, respectively, and transactivated these two genes, indicating the involvement of +-MITF in their expression. Because TPH is the rate-limiting enzyme for serotonin synthesis, we examined the serotonin content of +/+ and mi/mi CMCs. The serotonin content was significantly smaller in mi/mi CMCs than in +/+ CMCs. The introduction of +-MITF but not of mi-MITF normalized the serotonin content in mi/mi CMCs.

Animals↗

PubMed1998

Increase of mast cells in the liver and lung may be associated with but not a cause of fibrosis: demonstration using mast cell-deficient Ws/Ws rats.

Tissue fibrosis is frequently associated with an increase of mast cells, and mast cells are regarded as playing a role in the induction of tissue fibrosis. We attempted to examine whether mast cells influenced the induction of fibrosis using Ws/Ws mast cell-deficient rats. The mast cell deficiency of Ws/Ws rats is due to a 12-base pair deletion of the c-kit gene. The activity of c-kit receptor tyrosine kinase is remarkably reduced in Ws/Ws rats. Liver fibrosis was induced by the repeated injections of pig serum, and lung fibrosis was induced by the instillation of bleomycin. Marked fibrosis in the liver and lung did occur in the Ws/Ws rats, and the magnitude of fibrosis was more severe in Ws/Ws rats than in control normal (+/+) rats. The mast cell increase was observed in the liver of +/+ and Ws/Ws rats and in the lung of +/+ rats. However, the number of mast cells in the liver of treated Ws/Ws rats with marked fibrosis was comparable to that observed in the liver of nontreated +/+ rats without fibrosis. Histamine content increased in the liver and lung of +/+ rats after the treatment, but it remained in low levels even after the treatment in Ws/Ws rats. Mast cells and histamine did not appear to play important roles in the induction of fibrosis. Thus, an increase in mast cell number and histamine content may be associated with but not a cause of fibrosis.

Animals↗

PubMed1997

Role of mast cell histamine in the formation of rat paw edema: a microdialysis study.

We determined the endogenous histamine concentration in the subplantar space of rat hind paws using an in vivo microdialysis technique. A microdialysis probe was implanted into the rat hind paw and the histamine content in dialysates was measured by high performance liquid chromatography-fluorometry. In wild type (+/+) rats, the histamine output (basal level 25.7 +/- 0.9 pmol/ml) increased 115-, 199- and 426-fold rapidly after subplantar injection of compound 48/80 at doses of 0.5, 5 and 50 microg/paw, respectively. In genetically mast cell-deficient (Ws/Ws) rats, the basal level of histamine was one third of that obtained from +/+ rats, and was not increased by compound 48/80 injection. With this treatment, marked, dose dependent, but relatively gradual development of the paw edema was found in +/+ rats. However, no edema formation was observed in Ws/Ws rats. Histological observations showed neither mast cells nor edema to be present in the paw skin of Ws/Ws rats. These findings indicate the critical role of histamine as a trigger for the development of edema in vivo. In addition, Ws/Ws rats will provide important information as to the roles of mast cells in the inflammatory response.

Animals↗

PubMed1996

Brain penetration of the histamine H3 receptor antagonists thioperamide and clobenpropit in rat and mouse, determined with ex vivo [125I]iodophenpropit binding.

We investigated the brain penetration of the histamine H3 receptor antagonists thioperamide and clobenpropit using ex vivo [125I]iodophenpropit binding. Homogenates of the rat cortex, striatum and mouse whole brain were prepared 1 h after subcutaneous injection of the H3 antagonists and incubated with [125I]iodophenpropit, a radiolabeled H3 receptor antagonist, to determine the H3 receptor occupancy. Specific [125I]iodophenpropit binding to the rat cortex and striatum was inhibited by thioperamide with IC30 values of 1.0 and 1.5 mg/kg, respectively. Clobenpropit also inhibited [125I]iodophenpropit binding, but was less potent (IC30: 18 and 19 mg/kg in the rat cortex and striatum, respectively) than thioperamide. Similar results were obtained in experiments with mouse whole brain (3.5 and 13 mg/kg for thioperamide and clobenpropit), indicating that there is no important species differences in the brain penetration of these drugs between rats and mice. These findings suggest that after peripheral injection both in rat and mouse thioperamide penetrates the blood-brain barrier more efficiently compared to clobenpropit.

Animals↗

PubMed1996

The brain histamine (HA) and pituitary luteinizing hormone (LH) levels in female rats anesthetized with ether on proestrus.

Levels of brain histamine (HA) and pituitary luteinizing hormone (LH) were determined in female rats anesthetized with ether in the afternoon of proestrus. The rats after 6-hr ether anesthesia had an average HA concentration higher than that of non-anesthetized rats in the hypothalamus, but not in the cortex or diencephalon. Ether-anesthetized rats also showed a higher LH level in the pituitary than that of non-anesthetized rats. These findings agree well with our previous observation of an inhibited ovulation associated with a decrease in serum LH in female rats anesthetized with ether in the afternoon of proestrus. Furthermore, it is suggested that the release of pituitary LH into the circulating blood is regulated by the level of HA in the hypothalamus.

Anesthesia↗

PubMed1996

Transient increase of blood histamine level induced by pentagastrin. Continuous monitoring by in vivo microdialysis.

BACKGROUND: Since few studies of (penta)gastrin-induced histamine release from the gastric mucosa into blood has been performed, an effect of pentagastrin on histamine level of rat blood was examined by using the in vivo microdialysis method. METHODS: Pentagastrin was perfused through the microdialysis probe implanted into the jugular vein of urethane-anesthetized rats or in urethane-anesthetized, totally gastrectomized rats, and dialysis samples of blood were concurrently collected. Histidine decarboxylase (HDC) activities and histamine contents in the glandular stomach and gastric acid output after pentagastrin stimulation were also investigated. RESULTS: Pentagastrin induced a transient increase of blood histamine in a dose-dependent manner but failed to cause any increase of blood histamine in the totally gastrectomized rat. Pentagastrin also induced increases of the HDC activity in the glandular stomach and of the gastric acid output. The peak histamine level in blood occurred 40 min after pentagastrin perfusion, whereas the peak acid secretion occurred after 80-120 min and then leveled off. CONCLUSIONS: The transient increase of blood histamine induced by pentagastrin is attributable to the histamine released from enterochromaffin-like cells and could be monitored by using the in vivo microdialysis method.

Animals↗

PubMed1995

Simultaneous determinations of histamine and N tau-methylhistamine by high-performance liquid chromatography-chemiluminescence coupled with immobilized diamine oxidase.

A method for the simultaneous determinations of histamine and its metabolite N tau-methylhistamine by HPLC-chemiluminescence coupled with immobilized diamine oxidase was developed. The method was based on the determination of chemiluminescence formed by the reaction of a luminol-ferricyanide mixture in alkaline medium with hydrogen peroxide which is one of the metabolic products of histamine and N tau-methylhistamine formed by diamine oxidase. HPLC with postcolumn derivatization resulted in good separation of the two amines and gave linear relationships between the concentrations of both and their chemiluminescence intensities. The lower limits of chemiluminescent detection of histamine and N tau-methylhistamine were 5 and 10 pmol, respectively. The immobilized column showed good operational stability for more than 1 month, during which period 200 samples were analyzed. With this system, the histamine contents of the cerebral cortex, forestomach, glandular stomach, and kidney of Wistar rats were found to be 0.30, 58, 396, and 2.4 nmol/g wet wt, respectively. These values are very similar to those determined by HPLC-fluorometry. The N tau-methylhistamine contents of these tissues were 0.36, 0.40, 0.72, and 3.8 nmol/g wet wt, respectively. This method will be useful for studying the roles of histamine in both brain and peripheral tissues.

Amine Oxidase (Copper-Containing)↗

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

Localization of histamine N-methyltransferase messenger RNA in human nasal mucosa.

BACKGROUND: Histamine is metabolized mainly by histamine N-methyltransferase (HMT) to N tau-methylhistamine in human nasal mucosa. Human HMT cDNA has been cloned and expressed in COS cells. The purpose of this study was to determine the localization of HMT METHODS: The fragment (nucleotide residues 430-1055) of human HMT cDNA was subcloned in a Bluescript vector (Stratagene, La Jolla, Calif.), and HMT sense anti-sense RNA probes were made with T7 and T3 RNA polymerases. In situ hybridization with digoxigenin-labeled RNA probes was performed on surgical specimens of human nasal turbinates. RESULTS: HMT mRNA was localized in cells in the epithelium and submucosa, and densely in endothelial cells of vessels. No HMT mRNA was identified in the submucosal glands. The presence of HMT mRNA was confirmed by Northern blot analysis, and HMT activities were also detected in nasal mucosa. CONCLUSION: Our study indicates that endothelium expresses HMT mRNA, whereas cells in the epithelium and submucosa, which remain unidentified, are an additional source of HMT mRNA.

Blotting, Northern↗

PubMed1995

Histamine N-methyltransferase inhibitor potentiates histamine- and antigen-induced airway microvascular leakage in guinea pigs.

BACKGROUND: Histamine N-methyltransferase (HMT) modulates histamine- and antigen-induced bronchoconstriction. However, it is unclear whether vascular permeability evoked by an allergic reaction can be exaggerated by inhibition of HMT activity. METHODS: We studied the effects of intravenously injected SKF 91488, a specific HMT inhibitor, on increases in plasma extravasation induced by intravenously injected histamine in unsensitized guinea pigs and by intravenously injected ovalbumin antigen in guinea pigs sensitized to ovalbumin in vivo with Evans blue dye as a marker. RESULTS: Pretreatment with SKF 91488 shifted, in a dose-dependent fashion, the dose-response curves of the leakage of dye to histamine to lower concentrations in the trachea, main bronchi, and nasal mucosa. Likewise, pretreatment with SKF 91488 (20 mg/kg intravenously) significantly increased the leakage of dye induced by ovalbumin antigen (200 micrograms/kg intravenously) in three parts of the airway (p < 0.05). In contrast to SKF 91488, intravenously injected aminoguanidine, a specific inhibitor of diamine oxidase (16 mg/kg intravenously), did not alter the leakage of dye induced by histamine (from 0.001 microgram/kg to 10 micrograms/kg intravenously) (p < 0.20). HMT activities were observed in the nasal mucosa, as well as in the trachea and main bronchi, as shown in a previous study. CONCLUSION: These findings suggest that HMT modulates the effects of exogenous histamine and endogenously released histamine induced by antigen challenge on plasma extravasation in the airway in guinea pigs in vivo.

Amine Oxidase (Copper-Containing)↗

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

The release and subsequent synthesis of histamine in a transfected subclone of rat basophilic leukemia cells that expresses human muscarinic m1 receptors.

Effects of carbachol and antigen (dinitrophenylated bovine serum albumin) on histamine release and histidine decarboxylase (HDC, the enzyme synthesizing histamine) activity were studied in 2H3-m1 cells, a subclone of rat basophilic leukemia cells that expresses human muscarinic m1 receptors through transfection with the gene. Carbachol stimulated the release of histamine and the activity of HDC with 30-50% the intensity of the maximal effect of the antigen. Pirenzepine, an m1 antagonist, inhibited these carbachol effects in a dose-dependent manner. The effect of the combination of carbachol and antigen on histamine release showed no additivity. These results indicate that these effects of carbachol are exerted via m1 receptors, and they suggest that the actions of carbachol and antigen on histamine release share a common pathway(s), and the release and synthesis of histamine have a positive relationship like in a feedback system.

Animals↗

PubMed1995

Effects of the histamine H3 agonist (R)-alpha-methylhistamine and the antagonist thioperamide in vitro on monoamine oxidase activity in the rat brain.

The effects of an H3 agonist, (R)-alpha-methylhistamine (alpha-MeHA), and an H3 antagonist, thioperamide, on monoamine oxidase (MAO) activity in rat hypothalamus were studied in vitro. Thioperamide was more potent in inhibiting MAO-B than MAO-A activity; MAO-B activity in rat hypothalamic homogenates was competitively inhibited by thioperamide with a Ki value of 175 micronM. From this in vitro experiment, the conversion of N-telemethylhistamine to N-tele-methylimidazoleacetic acid may be inhibited by thioperamide, suggesting that thioperamide may affect the regulation of histamine metabolism within histaminergic neurons. In contrast with the results obtained with thioperamide, alpha-MeHA inhibited MAO-A more potently than MAO-B activity; the Ki values for MAO-A and -B of hypothalamic homogenates were estimated to be 1.1 and 3.3 mM, respectively. The weak inhibitory effect of alpha-MeHA for MAO-B does not seem to be a major cause of changes in N-tele-methylhistamine concentrations.

Animals↗

PubMed1994

Antigen and thapsigargin promote influx of Ca2+ in rat basophilic RBL-2H3 cells by ostensibly similar mechanisms that allow filling of inositol 1,4,5-trisphosphate-sensitive and mitochondrial Ca2+ stores.

In single, Fura 2-loaded RBL-2H3 cells, antigen and thapsigargin depleted the same intracellular pool of Ca2+ in the absence of external Ca2+; provision of external Ca2+ induced immediate increases in levels of free Ca2+ ([Ca2+]i). These increases were dependent on the presence of external Ca2+ and, presumably, on influx of Ca2+ across the cell membrane. Both stimulants enhanced intracellular accumulation of 45Ca2+ through ostensibly similar mechanisms because accumulation was blocked to similar extents by various multivalent cations or by depolarization with K+. Because thapsigargin blocked reuptake of Ca2+ into inositol 1,4,5-trisphosphate sensitive stores, uptake occurred independently of the refilling of these stores. Uptake was dependent instead on sequestration of 45Ca2+ in a pool of high capacity that was insensitive to thapsigargin, caffeine, GTP and inositol 1,4,5-trisphosphate but sensitive to ionomycin and mitochondrial inhibitors. The existence of an inositol 1,4,5-trisphosphate-insensitive pool was also apparent in permeabilized cells; at 0.1 microM [Ca2+]i, uptake of 45Ca2+ was largely confined (> 80%) to the inositol 1,4,5-trisphosphate-sensitive pool, but at 2 microM [Ca2+]i uptake was largely (> 60%) into the inositol 1,4,5-trisphosphate-insensitive pool. Provision of mitochondrial inhibitors along with thapsigargin to block uptake into both pools, did not impair the thapsigargin-induced increase in [Ca2+]i or influx of Ca2+, as indicated by changes in Fura 2 fluorescence, but did block the intracellular accumulation of 45Ca2+. The studies illustrate the utility of simultaneous measurements of [Ca2+]i and 45Ca2+ uptake for a full accounting of Ca2+ homoeostasis as exemplified by the ability to distinguish between influx and mitochondrial uptake of Ca2+.

Animals↗

PubMed1994

Clobenpropit (VUF-9153), a new histamine H3 receptor antagonist, inhibits electrically induced convulsions in mice.

The effect of clobenpropit (VUF-9153), a new histamine H3 receptor antagonist, on electrically induced convulsions was studied in mice. Clobenpropit significantly and dose dependently decreased the duration of each convulsive phase. Its anticonvulsant effects were prevented by pretreatment with (R)-alpha-methylhistamine and imetit (VUF-8325), histamine H3 receptor agonists. These findings suggest that the effect of clobenpropit on electrically induced convulsions is due to an increase in endogenous histamine release in the brain, which is consistent with biochemical results that clobenpropit increased brain histidine decarboxylase activity dose dependently. The anticonvulsive effect of clobenpropit was antagonized by mepyramine, a histamine H1 receptor antagonist, but not by zolantidine, a histamine H2 receptor antagonist, indicating that histamine released by the anticonvulsant effect of clobenpropit interacts with histamine H1 receptors of postsynaptic neurons. The present findings of the effect of clobenpropit on electrically induced convulsions are fully consistent with those of thioperamide as described previously (Yokoyama et al., 1993, Eur. J. Pharmacol. 234, 129), supporting the hypothesis that the central histaminergic neuron system is involved in the inhibition of seizures.

Animals↗

PubMed1994

Involvement of apamin-sensitive K+ channels in antigen-induced spasm of guinea-pig isolated trachea.

1. In order to examine whether K+ channels play a role in antigen-induced airway responses, the effect of K+ channel blockers on antigen-induced airway smooth muscle contraction and mediator release was examined in vitro in guinea-pigs actively sensitized with ovalbumin (OA). 2. Tracheal strips from sensitized animals were suspended in organ baths under a resting tension of 1 g and isometric tension was continuously measured. Cumulative concentration-response curves to OA (0.1-1000 ng ml-1) or histamine (10 nM-1 mM) were obtained in the presence and absence of K+ channel blockers. 3. OA (10, 100 or 1000 ng ml-1) was incubated with minced lung tissues from the same animals for 15 min in the presence and absence of K+ channel blockers, and released histamine and leukotriene C4 (LTC4) in the incubating medium were measured. 4. Apamin, a small conductance Ca(2+)-activated K+ channel (PK,Ca) blocker, (0.1, 0.3 and 1 microM) significantly inhibited OA-induced smooth muscle contraction, while charybdotoxin (ChTX, 10 nM), an intermediate and large conductance PK,Ca blocker, and iberiotoxin (IbTX, 3 nM), a large conductance PK,Ca blocker, were without effect. Apamin (0.3 microM) had no effect on exogenously administered histamine-induced airway smooth muscle contraction, suggesting that the inhibition of OA-induced contraction by apamin did not occur at the smooth muscle level. 5. The inhibition of OA-induced contraction by apamin (0.3 microM) was not significantly affected by pretreatment with a leukotriene antagonist, ONO-1078 (10 microM), but was abolished by pretreatment with a histamine H1-receptor blocker, pyrilamine (1 microM). 6. Apamin by itself (up to 0.1 MicroM) had no effect on spontaneous histamine release from minced lung tissues. Histamine release induced by low and intermediate concentrations of OA (10 and 100 ng ml-1)was significantly suppressed by apamin pretreatment (P<0.05 and P<0.001), whereas LTC4 release was not affected. ChTX (0.1 MicroM) and IbTX (10 nM) had no significant effect on either spontaneous or OA (100 ng ml-1)-induced histamine release.7. These results suggest that apamin partially but substantially inhibits antigen-induced smooth muscle contraction, presumably by inhibiting antigen-induced histamine release from airway mast cells through small conductance PKca closure.

Animals↗

PubMed1994

The disposition of thioperamide, a histamine H3-receptor antagonist, in rats.

An HPLC method using an ovomucoid-conjugated column has been developed for measurement of thioperamide, a histamine H3 antagonist, with a minimum quantitation limit of 0.05 micrograms mL-1. The assay was used to study the disposition of thioperamide in rats. After bolus intravenous administration of thioperamide (10 mg kg-1), the plasma concentration decreased monoexponentially with a half-life of 26.9 min. The apparent total body clearance of thioperamide from rat plasma was 74.6 mL min-1 kg-1. Although thioperamide was quickly transferred to various tissues, its concentrations in peripheral tissues were higher than that in the brain. However, the brain regional tissue/plasma ratios of thioperamide increased continuously after its injection.

Animals↗