Biomedical subjects

M Mio

Publications and source records attributed to M Mio.

At least 55 records · Page 3Linked to original sources

PubMed1991

Comparative study of the adverse effects of various radiographic contrast media, including ioversol, a new low-osmolarity medium. II. The complement system and endothelial cells.

The effects of ioversol, iohexol, iopamidol and meglumine sodium amidotrizoate (MSA) on the complement system and endothelial cells were investigated. The protein bindings of the radiographic contrast media (RCM), each tested with guinea pig plasma, were less than 1%. When guinea pig serum was incubated with any of the RCM, activation of the complement system, which leads to hemolysis, was not influenced by the nonionic agents, ioversol, iohexol or iopamidol. However, MSA, an ionic agent, significantly reduced hemolytic activity at 370 mgI/ml. Perfusion of the abdominal aorta with nonionic agents did not elicit significant endothelial damage; ioversol induced the least damage among the nonionic RCM, while MSA caused remarkable endothelial damage. Although MSA caused a marked release of endothelin-1 from cultured endothelial cells obtained from porcine aorta, nonionic RCM did not induce significant endothelin-1 release; no influence was elicited by ioversol and iohexol caused a weak suppression, while iopamidol had the opposite effect. These results indicate that ioversol could be used as a safe contrast medium in intravascular administration.

Animals↗

PubMed1990

Histamine release induced by histone and related morphological changes in mast cells.

When isolated rat peritoneal mast cells were exposed to histone mixture, both histamine release and degranulation were evoked rapidly and dose-dependently at concentrations higher than 1 microgram/ml in a Ca-free medium. All of the histone subfractions (H1, H2A, H2B, H3 and H4) induced histamine release from mast cells in a Ca-free medium and, as in the case of histone mixture, the amount of histamine release was reduced by addition of Ca2+. By means of high-voltage electron microscopy, at least three types of degranulation were observed in mast cells exposed to histone mixture: (1) microfilament-associated degranulation, (2) extrusion of granules with the surrounding membrane, and (3) mass degranulation.

Animals↗

PubMed1990

Sequential analysis of histamine release and intracellular Ca2+ release from murine mast cells.

Stimulation of murine peritoneal mast cells with compound 48/80 at a concentration of 1 microgram/ml elicited rather slow histamine release; the onset of release was observed 5 s after stimulation, and it reached a plateau at about 60 s. Both inositol-1,4,5-trisphosphate (IP3) and inositol-1,4-bisphosphate (IP2) contents increased to their maximum 5 s after stimulation. The IP3 content decreased to the control level more rapidly than that of IP2. Changes in the intracellular Ca2+ concentration of the quin 2 loaded mast cells were determined using a video-intensified microscopy system. The fluorescence intensity due to Ca-quin 2 complex increased rapidly after 48/80 stimulation in a Ca-free medium and reached the maximum at about 6-7 s. It became clear that the increase in IP3 content and the resulting Ca2+ release from the intracellular Ca store precede histamine release from murine mast cells.

Animals↗

PubMed1990

Anti-platelet activating factor, anti-leukotriene D4 and some other antiallergic activities of mequitazine.

The bronchoconstrictions of guinea pigs elicited in vivo by leukotriene D4 (LTD4) and platelet activating factor (PAF) were inhibited by pretreatment with mequitazine (CAS 29216-28-2) (p.o.) in a dose-dependent manner at doses of 5-20 mg/kg. Mequitazine (0.5-50 nmol/l) also inhibited LTD4- and PAF- induced contractions of guinea pig tracheal chain. These results suggest that mequitazine possesses antagonistic activity for LTs and PAF; the effects of mequitazine against these two agonists were much more potent than those of ketotifen. The histamine release induced by either of compound 48/80, concanavalin A or A23187 was inhibited by mequitazine at concentrations ranging from 1 to 20 mumols/l. In the inhibition process, mequitazine may act not only to inhibit the Ca2+ release from intracellular Ca store of mast cells but also to stabilize the lipid bilayer of the cell membrane as shown in the order parameter and hypotonic hemolysis. From the present study, it was assumed that mequitazine may exert antiallergic activity by antagonizing LTs and PAF as well as by inhibiting histamine release from mast cells.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1990

Antiallergic effects of astemizole on immediate type hypersensitivity reactions.

Astemizole (0.5-5 mg/kg, p.o.) dose-dependently inhibited heterologous and homologous PCA reactions in rats at ID50 values of 1.48 mg/kg and 2.37 mg/kg, respectively. The inhibitory effect of astemizole on heterologous PCA was most remarkable when this compound was given p.o. 2 h prior to antigen challenge. Astemizole (0.1-5 mg/kg, p.o.) dose-dependently inhibited experimentally-induced asthma in guinea pigs at an ID50 of 0.86 mg/kg. Ex vivo, astemizole (0.5-5 mg/kg, p.o.) inhibited antigen-induced histamine release from lung pieces of sensitized guinea pigs. In in vitro experiments, the drug dose-dependently inhibited antigen-induced histamine and SRS-A releases from guinea pig lung pieces at concentrations of 0.05-10 microM. Furthermore, astemizole (0.1-10 microM) inhibited the histamine release induced by compound 48/80 and antigen-antibody reaction from rat peritoneal mast cells, and at 0.1-500 nM inhibited both leukotriene C4- and platelet-activating factor (PAF)-induced contraction of isolated guinea pig trachea at submicromolar concentrations. Astemizole not only inhibited 45Ca uptake into rat mast cells but also prevented the Ca2+ release from the intracellular Ca store induced by compound 48/80, although this compound did not affect the histamine release from permeabilized mast cells induced by Ca2+. Our results suggest that one of the antiallergic mechanisms of astemizole may be an inhibition of signal transduction from the mast cell membrane to the intracellular systems.

Airway Resistance↗

PubMed1989

Microfilament-associated degranulation of sensitized guinea-pig lung mast cells.

When sensitized guinea-pig lung mast cells were exposed to antigen, granules were pushed out on to the cell surface. Subsequently, thin filaments, some extending as long as 15 microns, were projected radially with the extruded granules. The latter became swollen in the extracellular medium and the elongated filaments became shorter, until, within 7-8 min, the granules were reincorporated into the cytoplasm. The time course of morphological changes corresponded approximately to that of changes in the intracellular Ca2+ concentrations. The filaments connecting the extruded granules to the cell surface were stained with rhodamine-phalloidin, indicating that they consisted mainly of actin.

Actin Cytoskeleton↗

PubMed1989

Excitatory effect of histamine on the arousal system and its inhibition by H1 blockers.

To clarify whether the sedative effect of H1 blockers is exerted in relation to H1 receptors in the brain, EEG activity recorded from the cortex and thalamus of rats was studied by power spectral analysis. EEG processing was performed by the FFT method and displayed as compressed spectral arrays. When a train of low frequency electrical stimulation was applied to the midbrain reticular formation of conscious rats, there was an increase in spectral power recorded at the cortex and thalamus, especially in the low frequency bands (0-6 Hz). The intraventricular administration of histamine suppressed the increase in power; this inhibition was antagonized by simultaneous administration of pyrilamine or diphenhydramine, though not in in combination with cimetidine or ranitidine. As in the case of histamine, the administration of 2-methylhistamine decreased power in the slow wave region, while administration of 4-methylhistamine did not. It was assumed that the arousal effect of histamine is exerted via H1 and not related to H2 receptors. Adverse effects of H1 blockers, such as drowsiness, may be caused by their inhibition of histamine's arousal effect.

Animals↗

PubMed1989

Influence of aging on the histamine release and membrane fluidity of rat peritoneal mast cells.

The maturational changes in the degree of homologous passive cutaneous anaphylaxis (PCA) and the histamine release from peritoneal mast cells induced by several secretagogues were studied using Wistar rats (4-40 weeks old). Although the increase in vascular permeability of the rat skin induced by intradermal injection of histamine did not change significantly from one maturation period to the next, 6- to 8-weeks old rats were both the most susceptible to PCA reactions and the most responsive to histamine-releasing stimuli. Among rats in this age group (6-8 weeks), the fluidity of the resting cell membrane and the extent of membrane fluidity increase in response to compound 48/80 were greatest. Analysis of the lipid composition of mast cells indicated that the ratio of cholesterol to phospholipids was lowest at the age of 6-8 weeks. From the present study, we concluded that the maturational changes in the extent of histamine release seem to be related to membrane fluidity, which has a profile similar to that of maturation.

Aging↗

PubMed1989

Microfilament-associated, local degranulation of rat peritoneal mast cells.

When compound 48/80 was applied by means of microelectrophoresis to the surface of a rat peritoneal mast cell, localized degranulation was observed in the area close to the microelectrode tip. The extruded granules were connected to the cell surface by filaments. The filaments were elongated radially and, in some occasions, projected to a length of 5 microns. A few minutes later, the length of the protruded filaments became shorter and shorter and, finally, the extruded granules were reincorporated into the cell. When rhodamine-phalloidin, an F-actin-specific dye, was perfused the extruded granules and filaments were stained by this dye. This indicates that actin filaments or fragments of them exist on the granule surface and on the cell surface at the site of degranulation. These actin filaments bound to the mast cell granules may play an important role, not only for the extrusion of the granules, but also for the reuptake of extruded granules into the cytoplasm.

Actin Cytoskeleton↗

PubMed1988

Anti-allergic constituents in the culture medium of Ganoderma lucidum. (I). Inhibitory effect of oleic acid on histamine release.

The chloroform extract from Ganoderma lucidum broth markedly inhibited histamine release from rat peritoneal mast cells. From the active fractions, palmitic acid, stearic acid, oleic acid and linoleic acid were isolated. Oleic acid dose-dependently inhibited the histamine release and 45Ca uptake into mast cells induced by compound 48/80 and A-23187 at concentrations of 5 to 50 microM and 0.5 to 5 microM, respectively. Saturated fatty acids, however, had only a weak inhibitory effect on histamine release. Although linoleic acid and linolenic acid effectively prevented this release, these two compounds caused marked release at concentrations higher than 10 microM and 20 microM, respectively. Oleic acid induces membrane-stabilization in model membrane systems. It was concluded that one of the effective constituents obtainable from the chloroform extract of G. lucidum-cultured broth is oleic acid.

Animals↗

PubMed1988

Anti-allergic constituents in the culture medium of Ganoderma lucidum. (II). The inhibitory effect of cyclooctasulfur on histamine release.

For centuries, Ganoderma lucidum has been used in Oriental medicine for the treatment of chronic bronchitis. Sequential fractions of the culture medium of this plant revealed that one of the active constituents was cyclooctasulfur. The latter effectively inhibited histamine release from rat peritoneal mast cells and impeded 45Ca uptake into these cells without affecting the cyclic AMP content. SDS-PAGE analysis indicated that cyclooctasulfur induced some changes in protein bands obtained from the membrane fraction of mast cells, suggesting that this compound interacts with membrane proteins so as to inhibit 45Ca uptake, and that this may be the main cause of histamine release inhibition.

Animals↗

PubMed1988

Role of microfilaments in the exocytosis of rat peritoneal mast cells.

When rat peritoneal mast cells were treated with the potent histamine releaser compound 48/80 in the presence of tetramethylrhodamine-labeled G-actin, the fluorescent G-actin particles were bound to the surface of extruded granules and to the cell surface. When rhodamine-phalloidin was incorporated into permeabilized rat mast cells in a Ca2+-free medium, rhodamine fluorescence was observed on the cell surface accompanied by serpentine ridges which appeared in the resting state. After perfusion with a cytosol-like solution containing Ca2+, rhodamine fluorescence appeared on the cell surface as a distinct network formation. In some cases, circular fluorescences which appeared to surround the extruded pores were observed in the cell membrane. These findings indicate the existence of actin filaments in the cell membrane and/or subplasmalemmal network. In whole-mount preparations, the granules were surrounded very densely with microfilaments of various widths. After exposure to compound 48/80, granules protruding through the cell membrane were wrapped in many filaments. The extruded granules located in the periphery of the cells were connected by many filamentous structures and disruptions in the middle of these connections were occasionally observed. In some cases, circular configurations of microfilaments were observed at the bottom of the extruded granules and in others dense gatherings of microfilaments were seen just beneath the granules, as if the latter were being pushed up and out of the cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗

PubMed1987

The role of intracellular Ca2+ in the degranulation of skinned mast cells.

The intracellular pH of rat peritoneal mast cells was slightly acidic and compound 48/80 induced a decrease in the cytoplasmic pH of these cells. By means of chemical skinning, it was revealed that perfusion with Ca2+ or inositol 1,4,5-trisphosphate (IP3) induced degranulation dose-dependently in mast cells at concentrations higher than 10 microM and 0.1 microM, respectively. Na+ was essential for the release of histamine from mast cells. An assay based on the binding of 45Ca to mast cell fragments revealed that the intracellular Ca store of the mast cell is located in the endoplasmic reticulum. IP3 liberated Ca from the endoplasmic reticulum.

Animals↗

PubMed1987

Inhibitory effects of oxatomide on intracellular Ca mobilization, Ca uptake and histamine release, using rat peritoneal mast cells.

Oxatomide at concentrations of 0.01-10 microM inhibited not only an increase in 45Ca uptake but also the intracellular Ca2+ release induced by compound 48/80 in rat peritoneal mast cells. At higher concentrations, ketotifen or other calcium antagonists caused similar inhibitory effects. However, the inhibitory effect of oxatomide on the 45Ca uptake into rat neonatal heart cells was much weaker than that of verapamil. Through image processing of quin 2-stained mast cells, it was revealed that oxatomide inhibited Ca2+ release from the intracellular store. Although oxatomide alone did not affect cAMP and cGMP contents in sensitized guinea pig lung samples, the drug effectively prevented changes in the nucleotide contents evoked by antigen challenge. These results suggest that the inhibitory effect of oxatomide on histamine release may be caused by a combination of prevention of Ca uptake, which is highly selective toward mast cells; inhibition of Ca2+ release from the intracellular Ca store, and elevation of the cAMP content in mast cells.

Aminoquinolines↗

PubMed1987

Antiallergic effects of terfenadine on immediate type hypersensitivity reactions.

Terfenadine dose-dependently inhibited rat homologous PCA (2.5-10 mg/kg, p.o.) and experimentally-induced asthma in guinea pigs (0.5-5 mg/kg, p.o.). Similarly, metabolites I and II dose-dependently inhibited experimentally-induced asthma but their respective potencies were approximately 1/2 and 1/15th that of terfenadine. These results suggest that the metabolites contribute to the antiallergic effects of terfenadine. In ex vivo, terfenadine (5-20 mg/kg, p.o.) also inhibited the release of both antigen-induced histamine and SRS-A from sensitized guinea pig lung samples and that of histamine from rat peritoneal mast cells. Terfenadine dose-dependently increased the cAMP content in rat mast cells and in the lungs; in the latter, the augmented cAMP is associated with an increase in adenylate cyclase activity, but not with the inhibition of phosphodiesterase activity. The above evidence indicates that the inhibitory effects of terfenadine on mediator release from mast cells are in some way related to its antiallergic effects, and that an elevated cAMP content may be effective to enhance mediator release inhibition.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1986

Changes in intracellular Ca2+ distribution of rat peritoneal mast cells before and after histamine release.

Rat peritoneal mast cells were stained with quin 2, a fluorescent Ca2+ chelator. By means of a fluorescence microscope and real time image processer, it was revealed that the fluorescence derived from the Ca-quin 2 complex was weak in the area occupied by the nucleus and distributed unevenly in the cytoplasm of the resting cells so as to encompass the individual granules. When compound 48/80 or substance P was added in a Ca-free medium, the fluorescence intensity of quin 2 increased markedly all over the cell, suggesting that a large amount of Ca2+ was released from intracellular Ca stores. The increase in the fluorescence intensity produced by compound 48/80 or substance P in a Ca-free medium was inhibited by pretreatment with certain drugs eliciting an increase of c-AMP levels, such as dibutyryl c-AMP and theophylline, or by some anti-allergic drugs providing a membrane stabilizing action.

Aminoquinolines↗

PubMed1986

Intracellular calcium release induced by histamine releasers and its inhibition by some antiallergic drugs.

When rat mast cells loaded with fluorescent Ca2+ indicator Quin 2 were exposed to either compound 48/80 (0.1 micrograms/mL) or substance P (2 microM) at 37 degrees C for 30 seconds in a Ca-free medium, a marked increase of Quin 2 fluorescence was noticed, indicating that Ca2+ was released from the intracellular Ca store. The pixel values of the whole cell image were displayed in a three dimensional projection. When mast cells were exposed to 48/80, the fluorescent increase was reflected as an increase of height and spreading of the image. When 0.01 to 1 mM of db-cAMP was pretreated for five minutes, an increase of Quin 2 fluorescence was inhibited in a dose-dependent fashion. Theophylline pretreatment also showed a preventive effect at 1 to 5 mM. A marked inhibition of the Quin 2 signal was induced by pretreatment with 0.01 mM of terfenadine (63.4% inhibition) or ketotifen (26.6% inhibition). Disodium cromoglycate also showed a similar inhibitory effect. In the measurement of the order parameters of liposomes, the addition of either terfenadine or ketotifen into the lipids increased the parameter value, indicating they provide the membrane stabilizing action.

Aminoquinolines↗

PubMed1985

Analysis of the mechanism of histamine release induced by substance P.

Substance P causes release of histamine from rat peritoneal mast cells; the structure-activity relationship shows that N-terminal residue is essential and the hydrophobic region of C-terminal plays an important role. Electrical conductivity of black lipid membrane containing phosphatidic acid was augmented by substance P. In this case, N-terminal residues and C-terminal hydrophobicity were also unavoidable. The partitioning of substance P into the organic phase increased in the presence of phosphatidic acid. The CD spectrum of substance P was changed from the unordered form to beta-form by coexistence of phosphatidic acid/PC liposomes in the medium. The addition of calcium or magnesium in the test solution is effective to prevent either of these phenomena. These findings indicate that substance P probably binds to negatively charged sites of membrane lipids, and subsequent penetration of C-terminal into the hydrophobic core of lipid bilayer may induce an increase of membrane permeability and the following histamine release.

Animals↗