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Biomedical subjects

M Mio

Publications and source records attributed to M Mio.

At least 19 recordsLinked to original sources
PubMed1999

Ultraviolet B (UVB) light-induced histamine release from rat peritoneal mast cells and its augmentation by certain phenothiazine compounds.

When rat peritoneal mast cells were exposed to ultraviolet (UV) light (UVA, UVB and UVC), histamine release was evoked in a dose (intensity X time) dependent manner. The potency order of UV light in inducing the histamine release was UVC > UVB >> UVA. In this study, we focused on the effect of ultraviolet B (UVB) on histamine release from rat mast cells. The UVB-induced histamine release occurred at doses higher than 7.8 kJ m(-2), even at 4 degrees C. At a UVB dose of 18.8 kJ m(-2), where a 51.9+/-4.8% histamine release and a 58.8+/-6.8% degranulation took place, Trypan blue-stained cells accounted for 14.4+/-1.3% of the cells, and the lactate dehydrogenase (LDH) release was about 4.9+/-2.8%. This suggests that the membrane permeability to low molecular weight substances was increased by UVB exposure. The UVB-induced histamine release was inhibited by ascorbic acid at concentrations higher than 500 microM, suggesting the involvement of a radical reaction in the process. The UVB-induced histamine release was enhanced by some phenothiazine compounds, i.e., promethazine, trimeprazine, mequitazine, chlorpromazine, trifluoperazine, ethopropazine and thioridazine. We conclude that the phototoxicity of phenothiazine compounds may be due in part to an enhancement of UVB-induced histamine release from mast cells.

Adjuvants, Immunologic↗
PubMed1997

Histamine-induced cortisol secretion from bovine adrenocortical cells: co-incubated with bovine adrenal medullary cells.

Histamine at concentrations higher than 10(-9) M significantly elicited cortisol secretion from bovine adrenocortical (BAC) cells co-incubated with bovine adrenal medullary (BAM) cells, suggesting that BAM cells are responsible for histamine-induced cortisol secretion. Cortisol secretion from BAC cells co-incubated with BAM cells was also elicited by both an H1 agonist, 2-methylhistamine, and an H2 agonist, 4-methylhistamine. However, 4-methylhistamine was much less effective than 2-methylhistamine. Histamine-induced cortisol secretion was inhibited not only by H1 antagonists (pyrilamine and diphenhydramine) but also by H2 antagonists (cimetidine and ranitidine). Histamine effectively increased 45Ca uptake and IP3 production in BAM cells. These responses were antagonized by the H1 antagonist but not by the H2 antagonist. Histamine-induced cortisol secretion from BAC cells co-incubated with BAM cells was inhibited by beta-adrenoceptor antagonists, propranolol and timolol, as well as an NK1-receptor antagonist, D-Arg1-D-Trp7,9-Leu11-substance P. These results indicate that histamine can induce cortisol secretion from BAC cells at physiological concentrations through H1 receptors on BAM cells, and catecholamine and substance P may participate in histamine-induced cortisol secretion.

Adrenal Cortex↗
PubMed1997

Effect of an active metabolite of the antiallergic agent tazanolast on histamine release from rat mast cells.

WP-871 (3'-(1H-tetrazol-5-yl)oxanilic acid monohydrate, CAS 114607-46-4) is a monohydrate of a main active metabolite of tazanolast (butyl 3'-(1H-tetrazol-5-yl) oxanilate, CAS 82989-25-1), an orally active antiallergic drug. WP-871 inhibited dose-dependently compound 48/80-induced histamine release from rat peritoneal mast cells. In a similar dose range, WP-871 was effective in inhibiting compound 48/80-induced 45Ca uptake into mast cells from extracellular medium and compound 48/80-induced translocation of protein kinase C from the cytosol to the membrane fraction of mast cells. WP-871 also inhibited inositol trisphosphate production but did not exhibit a direct inhibitory effect on phospholipase C in mast cells. WP-871 caused no increase in cAMP content in mast cells. These results suggest that WP-871 may inhibit histamine release mainly by preventing the increase in intracellular Ca2+ concentration, which is a critical event in signal transduction leading to histamine release in mast cells.

Animals↗
PubMed1995

Effect of loratadine on immediate and delayed type hypersensitivity reactions.

Loratadine (CAS 79794-75-5) was effective in inhibiting the contractions of the ileum induced by histamine in guinea pigs. The drug also caused an anti-acetylcholine, anti-serotonin and anti-leukotriene D4 (LTD4) effect. In addition, loratadine inhibited the synthesis of leukotrienes more potently than ketotifen. On the other hand, in in vitro studies of histamine release from rat peritoneal mast cells induced by compound 48/80 or lung fragments in actively sensitized guinea, pigs, loratadine elicited a significant inhibition at a concentration of 5 mumol/l. In ex vivo studies, the drug inhibited histamine release from lung fragments induced by concanavalin A, and significant effect lasted for 24 h when the drug was administered at a dose of 20 mg/kg. The drug inhibited LTD4 release as well as histamine from lung fragments in actively sensitized guinea pigs. Loratadine inhibited not only 45Ca uptake into the rat peritoneal mast cells but also Ca2+ release from the intracellular Ca store induced by compound 48/80 or A23187. Loratadine increased cAMP content in rat lung preparation while decreasing cGMP content. Loratadine caused no significant change in order parameter and phospholipase A2 activity. The drug was more potent than ketotifen and terfenadine in inhibiting antigen-induced increase in airway resistance in guinea pigs. In addition, the effect of loratadine on airway resistance was sustained for 12 h. Loratadine inhibited an increase in dye leakage into the nasal cavity in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Inhibitory effect of interleukin-2 on histamine release from rat mast cells.

Interleukin-2 (IL-2) inhibited histamine release from rat mast cells induced by compound 48/80 in a concentration-dependent manner. The inhibitory effect of IL-2 on histamine release was also dependent on the length of the incubation period; the maximum inhibition was achieved at 8 h after IL-2 addition. Furthermore, IL-2 inhibited not only IP3 production but also 45Ca uptake in mast cells stimulated by compound 48/80. Since IL-2 enhanced [3H]-leucine uptake into mast cells, this suggests that protein synthesis may be related in some way with the inhibition of histamine release. IL-2 treatment augmented the synthesis of a protein having a molecular weight of approximately 35 kDa. From Western blotting analysis, it became clear that the production of lipocortin-I was augmented in rat mast cells by IL-2 treatment. The present study shows that IL-2 induces the synthesis of lipocortin-I in mast cells and that lipocortin-I may play some role in inhibiting histamine release from mast cells.

Animals↗
PubMed1994

Lateral movement of mast cell surface protein detected by gold-labeled anti-IgE and its relation with fodrin.

Rat mast cells were incubated with gold-conjugated concanavalin A and the movement of gold particles was observed using a polarization microscope. In resting cells, the movement of gold particles was very slow. When cells were stimulated with compound 48/80, the gold particles rapidly moved laterally, unrelated to granule extrusion. When sensitized mast cells were stimulated with gold-conjugated anti-IgE (anti-IgE-gold), patching of anti-IgE-gold was also observed. Immunofluorescence microscopy of rat mast cells stained with anti-fodrin antibody and rhodamine-phalloidin revealed that both fodrin and actin exist beneath the cell membrane forming a complicated network. After stimulation of the cells with anti-IgE-gold, the fodrin network was disrupted and thin fluorescence was observed homogeneously on the cell surface. By means of Western blotting, alpha-fodrin was detected in the membrane fraction of mast cells at the 240 kDa protein band. From the present study, it is suggested that disruption of the fodrin network may occur in association with the process leading to mast cell degranulation.

Animals↗
PubMed1994

Histamine-induced bi-directional differentiation of HL-60 cells towards neutrophils and eosinophils.

HL-60 cells, treated under alkaline conditions (pH 7.6) or acidic conditions (pH 7.2) for 2 months, were stimulated with histamine for 7 days. From the morphological examination and cytochemical characterization, it became clear that one of the clones treated in acidic pH differentiated to neutrophils and the other clone treated in alkaline medium differentiated to eosinophils after histamine-stimulation. The growth curve reached a maximum 4 days after stimulation. By means of in situ hybridization, it has been shown that the mRNA of major basic protein increased after histamine treatment only in the eosinophilic subclone, starting 4 days after stimulation. From the present study, it is suggested that when HL-60 cells were cultured under different pH conditions, commitment of lineages to the direction of either eosinophils or neutrophils takes place. Histamine may potently stimulate the further differentiation of both eosinophilic and neutrophilic clones.

Base Sequence↗
PubMed1994

Reinforcement effect of histamine on the differentiation of murine myeloblasts and promyelocytes: externalization of granulocyte colony-stimulating factor receptors induced by histamine.

Histamine and recombinant granulocyte colony-stimulating factor (rG-CSF) stimulated the differentiation of murine myeloblasts and promyelocytes to mature neutrophils. In connection with this, myeloperoxidase activity of these progenitor cells was decreased by either histamine or rG-CSF treatment. After pretreatment with histamine at 1 microM, both differentiation and the decrease in myeloperoxidase activity of myeloblasts and promyelocytes induced by rG-CSF were significantly augmented. Binding assays using 125I-labeled rG-CSF showed that the number of rG-CSF binding sites on the surface of neutrophil progenitor cells increased after histamine treatment. The histamine-induced increase in rG-CSF binding appeared to be definitely through H2 receptors. Furthermore, the increase in rG-CSF binding sites due to histamine treatment seemed to take place in association with the externalization of G-CSF receptors, because 1) the binding increase was observed in the presence of cycloheximide, 2) no concomitant increase in [3H]leucine uptake was elicited, and 3) colchicine and cytochalasin D effectively prevented the increase in rG-CSF binding due to histamine. In neutrophil progenitors, cAMP contents increased very rapidly and significantly after either histamine or rG-CSF treatment. Moreover, dibutyryl-cAMP increased rG-CSF binding to neutrophil progenitor cells in a dose-dependent fashion. However, when progenitor cells were pretreated with protein kinase A inhibitors, the histamine-induced increase in rG-CSF binding was remarkably decreased. This result seems to indicate that the stimulatory effects of histamine on rG-CSF binding to progenitor cells are intimately related to the cAMP-protein kinase A system in neutrophil progenitors. Moreover, c-myc mRNA expression in neutrophil progenitors was markedly reduced by either histamine or rG-CSF treatment. It was concluded that rG-CSF-induced differentiation of murine neutrophil progenitors was augmented by histamine pretreatment mainly due to an increase in rG-CSF receptors on these cells and this increase might be related to the externalization of rG-CSF receptors.

Animals↗
PubMed1993

The pathway responsible for EEG synchronization and effect of histamine on this system.

Electrical stimulation (3 Hz, 0.5 volts) to the midbrain reticular formation of conscious rats induced significant increase of EEG power densities (synchronization) recorded at the frontal cortex (FCOR), nucleus ventralis thalami (VE), or nucleus medialis centralis thalami (CM). Significant synchronization was also observed in the FCOR when electrical stimulation was applied to the VE and CM. When ipsilateral and bilateral VEs were electrocoagulated, no EEG synchronization was observed in the FCOR and CM. Intracerebroventricular administration of histamine (Hi) caused a marked suppression of FCOR EEG synchronization in both CM-lesioned and normal rats through H1 receptors. EEG synchronization in FCOR was not induced in ipsilateral or bilateral VE-lesioned rats after RF stimulation. When Hi (1 microgram) was injected into the VE of normal rats, EEG synchronization of FCOR was markedly reduced after RF or VE stimulation. No such changes were induced when Hi was injected into the CM.

Animals↗
PubMed1993

Ca(2+)-induced cortisol secretion from permeabilized bovine adrenocortical cells: the roles of calmodulin, protein kinase C and cyclic AMP.

In order to clarify the role of intracellular second messenger systems in the cortisol secretion from bovine adrenocortical (BAC) cells, the cells were permeabilized with beta-escin and stimulated intracellularly with various compounds. When the permeabilized BAC cells were exposed to submicromolar concentrations of Ca2+, a prompt cortisol secretion was elicited in a concentration-dependent manner. As the cells were stimulated with 12-O-tetradecanoyl-phorbol-13-acetate and 1-oleoyl-2-acetyl-glycerol, slow but persistent cortisol secretion was elicited, but in the case of 4 alpha-phorbol-12,13-didecanoate, no such effect was observed. The Ca(2+)-induced cortisol secretion was inhibited by simultaneous applications of calmodulin and protein kinase C (C kinase) inhibitors, but no significant inhibition was elicited by protein kinase A (A kinase) inhibitor. The results seem to indicate that in the Ca(2+)-induced cortisol secretion calmodulin may stimulate the initial stage, while C kinase may be involved mainly in the late phase of the secretion. In addition, cyclic AMP (cAMP) was also effective in activating cortisol secretion from permeabilized BAC cells. The cAMP-induced cortisol secretion was suppressed by an A kinase inhibitor but not affected by calmodulin or C kinase inhibitor. When Ca2+ and cAMP were added simultaneously at concentrations lower than those required to induce the cortisol secretion separately, a marked cortisol secretion was elicited, suggesting that a synergic action exists between Ca(2+)- and cAMP-activated systems. The Ca(2+)-induced cortisol secretion was suppressed by ruthenium red, an inhibitor of Ca2+ transport in the mitochondria. Although both NADP+ and NADPH elicited only a transient cortisol secretion, simultaneous addition of Ca2+ with NADP+ or NADPH caused a potent and sustained cortisol secretion. The augmentation due to Ca2+ on the NADP+ (or NADPH)-induced cortisol secretion was inhibited by the addition of a calmodulin inhibitor or a C kinase inhibitor, but not such effect was caused by A kinase inhibitor. From the present investigation, it was concluded that the Ca(2+)-dependent intracellular signal transduction may simulate the cortisol synthesis systems in the mitochondria of BAC cells.

Adrenal Cortex↗
PubMed1993

Inhibitory effects of emedastine difumarate on histamine release.

The inhibitory effects of emedastine difumarate on histamine release were studied in rat peritoneal mast cells. Emedastine significantly inhibited substance P (SP)-induced histamine release at concentrations above 10(-9) M in the presence of extracellular Ca2+ and at concentrations above 10(-11) M in its absence. At concentrations of 10(-8) M or higher, emedastine significantly inhibited SP-induced Ca2+ release from intracellular Ca stores and SP-induced 45Ca uptake into mast cells. Emedastine also inhibited passive peritoneal anaphylaxis in rats and guinea pigs. We conclude that the clinical antiallergic effects of emedastine involve the inhibition of histamine release and that this inhibition is mediated by the inhibition of Ca2+ release from intracellular Ca stores and the inhibition of Ca2+ influx into mast cells.

Anaphylaxis↗
PubMed1993

Antiallergic profile of the novel H1-antihistaminic compound levocabastine.

Levocabastine hydrochloride (R50 547, CAS79516-68-0) caused no inhibitory effect on the histamine release from rat peritoneal mast cells induced by compound 48/80, A23187 and concanavalin A. However, the drug inhibited histamine release from passively sensitized mast cells and passive peritoneal anaphylaxis in rats, though higher concentrations or doses were required. Moreover, levocabastine provided a relatively potent inhibitory effect on histamine release from lung pieces of actively sensitized guinea pigs exposed to antigen, and simultaneously the drug prevented a decrease in the cyclic AMP (cAMP) content. Levocabastine potently inhibited histamine-induced cutaneous reactions in rats and the drug also prevented histamine-induced contraction of isolated guinea pig ileum. Levocabastine did not induce any significant changes in platelet aggregation or in the contraction of guinea pig ileum induced by platelet activating factor (PAF). However, the drug inhibited eosinophil migration induced by PAF. The chemotaxis of neutrophils induced by N-formyl-methionyl-leucylphenylalanine (fMLP) was also inhibited by levocabastine in a dose-dependent fashion. Levocabastine has no influence on the order parameter tested with liposomes, suggesting that the drug provides no significant effect on the membrane fluidity of lipid bilayer. These results seem to indicate that the antiallergic effect of levocabastine is mainly dependent on its potent antihistaminic activity.

Anaphylaxis↗
PubMed1993

Histamine-induced production of interleukin-1 alpha from murine bone marrow stromal cells and its inhibition by H2 blockers.

In this study, the role of histamine in interleukin-1 (IL-1) formation in murine bone marrow stromal cells was investigated in vitro. It was found that histamine and 4-methylhistamine increased the number of granulocyte colony-forming units in murine bone marrow cells. A similar effect was elicited by dibutyryl-cAMP and theophylline. When histamine and H2 agonists, such as 4-methylhistamine and dimaprit, were added to the culture medium containing murine bone marrow stromal cells, thymocyte comitogenic activity detected in the medium increased significantly. However, no such effect was observed in the case of 2-methyl-histamine, an H1 agonist. Histamine-induced production of thymocyte comitogenic activity in bone marrow stromal cells was inhibited by some H2 antagonists, such as cimetidine, ranitidine, and famotidine, but not by the H1 antagonist pyrilamine. Histamine was also effective in inducing the colony-promoting activity in murine bone marrow stromal cells. This was also inhibited by H2 antagonists such as cimetidine, ranitidine, and famotidine. Histamine elicited an increase in cAMP content in bone marrow stromal cells. From gel filtration analysis, the molecular mass of the active substance produced by bone marrow stromal cells in response to histamine was in the range of 15 to 20 kDa. By means of Western blotting analysis, it was found that production of pro-IL-1 alpha in the bone marrow stromal cells was induced by histamine. The production of pro-IL-1 alpha in bone marrow stromal cells stimulated by histamine was inhibited not only by H2 antagonists, such as cimetidine, ranitidine, and famotidine, but also by the protein kinase A antagonist KT-5720. These results indicate that histamine stimulates the production of IL-1 alpha in bone marrow stromal cells and that this results in the proliferation and differentiation of neutrophil progenitor cells.

Animals↗
PubMed1992

de novo synthesis of calmodulin binding protein in substance P-induced steroidogenesis in bovine adrenocortical cells.

In order to clarify the mechanism of substance P (SP)-induced cortisol secretion from bovine adrenocortical (BAC) cells, protein synthesis at the early stage of SP-stimulation in BAC cells was investigated. Both SP and adrenocorticotropic hormone (ACTH) increased [3H]leucine uptake into BAC cells in a dose-dependent fashion. Although the SP-induced [3H]leucine uptake precedes the cortisol secretion, ACTH was slower in inducing [3H]leucine uptake and cortisol secretion. Protein synthesis inhibitors, actinomycin D and cycloheximide, were potent in inhibiting the SP-induced cortisol secretion. SDS-PAGE analysis, revealed that a 240 kDa protein is newly synthesized in BAC cells in response to SP but not ACTH. It was also indicated that the production of this 240 kDa protein was elicited about 30 min after stimulation by SP. Moreover, A23187 and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) also caused a rapid [3H]leucine uptake and production of 240 kDa protein. In contrast, dibutyryl cAMP did not induce the synthesis of this 240 kDa protein. Calmidazolium, a calmodulin inhibitor, effectively inhibited not only [3H]leucine uptake but also 240 kDa protein production due to SP. On the other hand, KT-5720, an inhibitor of protein kinase A, had no effect on [3H]leucine uptake or 240 kDa production. Using the [125I]calmodulin-membrane overlay method, it was found that the 240 kDa protein was a newly synthesized calmodulin binding protein. From the present study, it was concluded that the de novo synthesis of this 240 kDa protein may be intimately related to the cortisol secretion in SP-stimulated BAC cells associated with an activation of the Ca-calmodulin pathway.

Adrenal Cortex↗
PubMed1992

Histamine-induced differentiation of HL-60 cells. The role of cAMP and protein kinase A.

When HL-60 cells were stimulated with histamine, a significant differentiation of the cells toward neutrophils was elicited. Histamine increased phagocytic activity, but it reduced myeloperoxidase activity of HL-60 cells. Histamine-induced differentiation in HL-60 cells was inhibited not only by H2 antagonists, such as cimetidine, ranitidine and famotidine, but also by an inhibitor of protein kinase A (A kinase), KT-5720. Histamine increased the cAMP level and A kinase activity in HL-60 cells; both increases preceded the cell differentiation. Histamine also enhanced phosphorylation of a 160 kD protein in HL-60 cells, while H2 antagonists and KT-5720 inhibited this phosphorylation. The results of the present study indicate that an activation of A kinase via H2 receptor stimulation may cause the phosphorylation of a 160 kD protein and that this phosphorylation is probably involved in the process leading to differentiation of HL-60 cells.

Carbazoles↗