Biomedical subjects

K Tasaka

Publications and source records attributed to K Tasaka.

At least 145 records · Page 8Linked to original sources

PubMed1991

Essential role of ATP and possibility of activation of protein kinase C in Ca(2+)-dependent histamine release from permeabilized rat peritoneal mast cells.

To elucidate the role of ATP in histamine release, the present study was performed using beta-escin-permeabilized rat peritoneal mast cells. Ca(2+)-induced histamine release from permeabilized cells is totally dependent upon exogenous ATP in the medium. In the presence of Ca2+, ATP caused histamine release concentration-dependently at concentrations ranging from 0.01 to 5 mmol/l. The maximum release was achieved at 3 mmol/l of ATP in the medium. When the other adenosine nucleotides (AMP, ADP), or nonhydrolyzable ATP analogues (adenylylimidodiphosphate, beta, gamma-methylene ATP) were added in place to ATP, no histamine release took place. Other ribonucleoside triphosphates (GTP, ITP, UTP and CTP) had little effect at the same concentration range. When the ribonucleoside triphosphate content of mast cells was determined by means of HPLC, ITP and CTP were not detectable. A millimolar range of the ATP content was determined in mast cells, but the amounts of other ribonucleoside triphosphates (GTP and UTP) were remarkably lower than that of ATP. These results seem to indicate that the ATP molecule plays a crucial role in histamine release from rat mast cells in association with its concurrent hydrolysis. Furthermore, 12-O-tetradecanoylphorbol-13-acetate and 1-oleoyl-2-acetylglycerol enhanced histamine release elicited in the presence of Ca2+ (0.1 mumol/l) and ATP (3 mmol/l). Calphostin C, a potent inhibitor of protein kinase C, inhibited Ca2+/ATP-dependent histamine release by approximately 60%. At the same concentration, calphostin C inhibited by 95% protein kinase C activity in the crude extract obtained from rat mast cells. It was suggested that protein kinase C activation took place in the Ca2+/ATP-dependent histamine release from permeabilized rat mast cells.

Adenosine Triphosphate↗

PubMed1991

Role of cytoskeletons on Ca2+ release from the intracellular Ca store of rat peritoneal mast cells.

Cytochalasin D, colchicine or vinblastine effectively inhibited both histamine release and 45Ca uptake induced by compound 48/80 in rat mast cells. The inhibitory effects of cytochalasin D or colchicine on histamine release were exerted more remarkably when permeabilized mast cells were stimulated with either Ca2+ or inositol-1,4,5-trisphosphate (IP3). Since colchicine, vinblastine or cytochalasin D were not effective in inhibiting IP3 formation, it was assumed that microtubules or microfilaments may not participate in the initial stages of the membrane events leading to histamine release. By contrast, in Ca2+ release from the intracellular Ca store both colchicine and vinblastine (but not cytochalasin D) were effective in inhibiting Ca2+ mobilization, indicating that microtubules, rather than microfilaments, are intimately related to Ca2+ release from the endoplasmic reticulum (ER). By means of a fluorescence microscope, it was revealed that colchicine decreased the fluorescence intensity of FITC-labeled anti-tubulin antibody in the mast cells, while the amount of tubulin polymer in mast cells increased after exposure to compound 48/80. The findings indicate that colchicine simply suppressed polymerization of tubulin, while the rearrangement of microtubules so as to increase the polymerization took place after exposure to compound 48/80. Using an electron microscope in combination with potassium antimonate technique, Ca-antimonate dots were clearly observed in a cluster on the surface of the ER and a distinct connection between the ER and microtubules was also observed. It was concluded that microtubules play an important role in the processes leading to Ca2+ release from the intracellular Ca store and in subsequent histamine release.

Animals↗

PubMed1991

Tumor necrosis factor-alpha stimulates prolactin release from anterior pituitary cells: a possible involvement of intracellular calcium mobilization.

We investigated the effects of tumor necrosis factor-alpha (TNF alpha), a cytokine produced as one aspect of inflammatory reactions, on the intracellular free calcium concentration in single pituitary cells using a calcium-sensitive fluorescent dye, indo-1, and a digital imaging fluorescence microscopic system. TNF alpha induced an increase in intracellular free calcium immediately after administration, reaching a peak after 30 sec and then returning to nearly the basal level after 120 sec in the pituitary cells. The cells responding to TNF alpha constitute about 15% of the pituitary cell population, and these cells never responded to the hypothalamic releasing hormones TRH, GnRH, GH-releasing hormone, or CRH. To define the role of calcium in TNF alpha-induced PRL release, dispersed pituitary cells were exposed to agents that modify TNF alpha-induced calcium mobilization. Such calcium channel blockers as cobalt and verapamil decreased basal and TNF alpha-induced PRL release. A low calcium medium also decreased TNF alpha-induced PRL release. These data suggest that intracellular calcium mobilization may be involved in the process of TNF alpha-induced PRL release.

Animals↗

PubMed1991

Inhibitory effect of levocabastine on experimental allergic conjunctivitis in guinea pigs.

The effect of levocabastine on allergic and histamine (Hi)-induced conjunctivitis in guinea pigs was compared with those of cromolyn sodium and amlexanox. Levocabastine inhibited both antigen- and Hi-induced conjunctivitis. Amlexanox had no effect on Hi-induced conjunctivitis; however, the drug elicited a significant inhibition of allergic conjunctivitis. On the other hand, the effect of cromolyn sodium was almost negligible in both cases. Levocabastine moderately inhibited Hi release from guinea pig conjunctiva induced by antigen-antibody reactions. Amlexanox also caused a significant inhibitory effect, whereas cromolyn sodium was not effective in suppressing Hi release induced by antigen challenge. Furthermore, levocabastine prevented an increase in the vascular permeability elicited by both Hi and antigen instillation.

Aminopyridines↗

PubMed1991

Comparative study of certain antibiotics on epileptogenic property, including (1Rpi, 5S, 6S)-2-[(6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazolium-6-yl)] thio-6-[(R)-1-hydroxyethyl]-1-methyl-carbapenem-3-carboxylate (LJC10627), a carbapenem antibiotic with broad antimicrobial spectrum.

The epileptogenic effects of (1R, 5S, 6S)-2-[(6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazolium-6- yl)]thio-6-[(R)-1-hydroxyethyl]-1-methyl-carbapenem-3-carboxylate (LJC10627), a new derivative of carbapenem were studied in comparison with those of imipenem (imipenem/cilastatin), cefazolin and penicillin G. In intraventricular injection in rats, LJC10627 caused no epileptogenic activity at a dose of 32 micrograms. In contrast, imipenem, cefazolin and penicillin G showed dose-related seizure signs, continuous rhythmic spikes or high voltage spike-wave complexes and convulsive behaviors at doses higher than 10 micrograms. After intravenous injection of LJC10627, no epileptogenic signs on the electroencephalogram (EEGs) or in behavioral symptoms were observed, even at a dose of 500 mg/kg in rats and 300 mg/kg in rabbits, respectively. By contrast, imipenem/cilastatin provoked severe seizure patterns characterized by high voltage spikes-wave complex and convulsive behavior, both in rats and rabbits, using the same doses of LJC10627. Cefazolin and penicillin G also induced obvious epileptogenic signs in both rats and rabbits after intravenous injection. From these results, it was concluded that LJC10627, unlike imipenem (imipenem/cilastatin) and cefazolin, dose not elicit epileptogenic activity, and may therefore be safely used for clinical purpose.

Animals↗

PubMed1991

[Recent advances in the research on histamine release].

An increase in inositol 1, 4, 5-trisphosphate (IP3) formation in rat mast cells precedes an elevation in intracellular Ca2+ levels, which triggers the process(es) leading to histamine release. By means of a transmission electron microscope, it was revealed that when permeabilized mast cells were exposed to potassium antimonate, antimonate precipitates in the endoplasmic reticulum (ER) in the form of calcium antimonate, indicating that the ER is the intracellular Ca store in rat mast cells. IP3 at concentrations higher than 0.5 microM preferentially releases Ca2+ from the isolated ER of mast cells. GTP was also effective in releasing Ca2+ from the ER. IP3-induced Ca2+ release was inhibited by pretreatments with cAMP and antiallergic drugs. An increase in the intracellular Ca2+ concentration may lead to an activation of calmodulin, C kinase and cytoskeletal elements in sequence. Furthermore, microtubules may play an important role in the process(es) leading to Ca2+ release from the intracellular Ca store and subsequent histamine release, without affecting IP3 formation. In contrast, microfilaments seem to participate not only in the extrusion but also in the reincorporation of the mast cell granules, having no influence on intracellular Ca2+ release. Substance P (SP) is one of the most effective neuropeptides for releasing histamine from mast cells. Structure-activity relationship studies indicate that basicity at the N-terminal and hydrophobicity at the C-terminal are requisite for its histamine releasing activity. SP effectively released Ca2+ from the intracellular Ca store. The site of action of SP on the mast cell surface seems to be the same as that of compound 48/80. Eosinophil major basic protein (MBP) and histone are also effective for releasing histamine. The cDNA sequences of two subclasses of guinea pig MBP have been determined. These proteins may be released at the site of inflammation from the cells activated by the chemical mediators released from mast cells, and consequently, mast cell activation was reinforced. Such cell-to-cell interaction may be the reason for the augmentation of inflammation.

Animals↗

PubMed1991

Participation of histamine in the step-through active avoidance response and its inhibition by H1-blockers.

The effects of intravenous and intracerebroventricular administrations of certain H1-blockers on the active avoidance response in rats were studied. Among the classic H1-blockers used in this study: pyrilamine, diphenydramine, promethazine and chlorpheniramine, promethazine was the most effective and chlorpheniramine the least in inhibiting the active avoidance response; namely, a variation of prolongation in the response latency of the avoidance response. Meanwhile, ketotifen most potently inhibited the active avoidance response when the drugs were administered intracerebroventricularly. Mequitazine, astemizole and oxatomide were weak depressants when administered by either route. Azelastine was less effective than the classic H1-blockers by intravenous injection, while by intracerebroventricular injection, the inhibition was almost identical to those induced by the classic H1-blockers. Intracerebroventricular injection of histamine was antagonized the prolonged latency in the avoidance response induced by pyrilamine or diphenhydramine. A similar effect was also produced by 2-methylhistamine, but 4-methylhistamine had no effect. Intracerebroventricular injection of acetylcholine was restored the retarded avoidance response induced by pyrilamine, but a dose 20 times greater than that of histamine was required. From these findings, it can be concluded that inhibition of the active avoidance response induced by H1-blockers may be exerted through interaction with H1-receptors in the brain.

Analysis of Variance↗

PubMed1991

Inhibitory effect of MY-1250 on histamine release from rat peritoneal mast cells and guinea pig lung fragments: the elucidation of the mechanism.

When the effect of MY-1250 (5,6-dihydro-7,8-dimethyl-4,5-dioxo-4 H-pyrano [3,2-c] quinoline-2-carboxylic acid) on histamine release from rat peritoneal mast cells induced by compound 48/80 was studied, MY-1250 caused a significant inhibition of histamine release at concentrations higher than 3 microM. Furthermore, the compound inhibited not only 45C a uptake into the mast cells but also Ca2+ release from the intracellular Ca store at a concentration of 10 microM in both cases. By contrast, MY-1250 did not affect either histamine release from permeabilized mast cells induced by TPA, IP3 and GTP gamma S or Ca2+ release from the endoplasmic reticulum induced by IP3. In the chopped lung preparations, MY-1250 at doses of 10 and 100 microM caused a significant inhibition in histamine release from the pieces of actively sensitized guinea pigs exposed to antigen and simultaneously prevented a decrease in intracellular cAMP contents taking place in association with antigen-antibody reaction. No significant changes were effected by MY-1250 in alpha-chymotrypsin activity and phospholipase A2 activity. Also, no antagonistic effects on LTD4 and PAF were observed.

Animals↗

PubMed1991

Two aspects of the excitatory influence of histamine on hippocampal neurons in guinea pigs.

The effect of histamine (Hi) on CA3 pyramidal cells in guinea pig hippocampal slices was studied by means of intracellular recordings in association with electrical stimulation to the mossy fibers of granular cells. The amplitude of EPSPs and spikes was augmented significantly by Hi at concentrations of 10(-7) to 10(-6) M. The stimulatory effect of Hi was mimicked by the H2-agonist dimaprit (10(-6) M), but not by the H1-agonist 2-thiazolylethylamine (10(-5) M). An increase in EPSPs or spikes was provoked during perfusion of dibutyryl cAMP at concentrations higher than 10(-6) M. Intracellular application of cAMP to the pyramidal cells augmented the amplitude of EPSPs. The amplitude of IPSPs provoked by GABA was reduced by simultaneous perfusion of Hi at concentrations of 10(-7) M to 10(-6) M. The Hi-induced reduction was not blocked by either pyrilamine, cimetidine or thioperamide. It became clear that Hi exerts an excitatory influence on the hippocampal neurons, not only by stimulating the excitatory system via an H2-receptor coupled with Hi-sensitive adenylate cyclase, but also by depressing the inhibitory system, which may be mediated by GABA.

Animals↗

PubMed1991

Inhibitory effect of epinastine on the type II-IV allergic reactions in mice, rats and guinea pigs.

The inhibitory effect of epinastine (WAL 801 CL, CAS 80012-43-7) on types II, III and IV allergic reactions was studied. Epinastine caused an inhibition of type II allergic reactions: 1. the swelling of rat foot pad induced by a subcutaneous injection of anti-rat rabbit antiserum, and 2. lethality induced by an intravenous injection of anti-SRBC (sheep red blood cells) rabbit serum into guinea pigs (Forssman systemic reaction). The drug also caused an inhibition of the early phase in active Arthus reaction in guinea pigs (type III reactions). However, no significant inhibition was detected in the delayed-hypersensitivity reaction (type IV allergic response) induced by sheep red blood cells or picryl chloride in mice.

Animals↗

PubMed1991

Comparison of pharmacological properties of optical isomers and a racemic mixture of epinastine.

Some pharmacological effects of d- and l-isomers of epinastine (WAL 801 CL, 3-amino-9,13b-dihydro-1H-dibenz [c,f]imidazo[1,5-a]azepine hydrochloride; CAS 80012-43-7) were studied in comparison with that of dl-epinastine. Although no significant difference was detected, d-epinastine is slightly more active than the l-isomer in the depressant actions of the central nervous system. However, in EEG power spectra recorded at the frontal cortex, occipital cortex, hippocampus and amygdala in conscious rats, no appreciable differences were recognized between two optical isomers and a racemic mixture. Furthermore, the extents of compound 48/80-induced lethality, antagonism on histamine-induced contraction of guinea pig ileum and histamine release from rat peritoneal mast cells were almost the same among the racemate and optical isomers of epinastine. In addition, two stereoisomers caused an almost equal degree of inhibition in antigen-induced histamine release from the lung pieces of sensitized guinea-pigs and the equivalent level of inhibition was exerted by the racemate.

Animals↗

PubMed1991

Antiallergic effects of major metabolites of astemizole in rats and guinea pigs.

Antiallergic effects of astemizole (CAS 68844-77-9) and its metabolites were studied using rats and guinea pigs. All the metabolites of astemizole tested i.e., desmethylastemizole, 6-hydroxydesmethylastemizole and norastemizole, were more active than astemizole in inhibiting the contraction of the ileum as well as the bronchoconstriction induced by histamine in guinea pigs. Desmethylastemizole was about the same as the parent compound in inhibiting the 3H-mepyramine binding in guinea pig cerebellum. In heterologous passive cutaneous anaphylaxis (PCA) and homologous PCA, the metabolites caused almost equipotent inhibition to that seen in astemizole. On the other hand, in the studies of histamine release from rat peritoneal mast cells induced by compound 48/80 or from lung fragments in actively sensitized guinea pigs, desmethylastemizole, 6-hydroxydesmethylastemizole and norastemizole were much less potent than was astemizole. No H2-antagonistic activity was observed with either astemizole or desmethylastemizole.

Animals↗

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↗

PubMed1991

[Analysis of mechanism of lung edema in E. coli injected septic rat model--in relation to tumor necrosis factor (TNF) produced from liver, spleen, and alveolar macrophages].

After injection of live E. coli, TNF in blood and culture supernatant of the isolated macrophages from the lung, liver, and spleen, were measured, and possible relationship between their TNF levels and lung edema was examined. The blood TNF activity increased significantly until 3h after the injection in the lethal group (p less than 0.01). The TNF activity of alveolar macrophages showed no changes even in the lethal group. The TNF activities of the liver and spleen macrophages decreased significantly in the lethal group (p less than 0.01-0.05), while those in the sublethal group that didn't induce lung edema and showed no significant decrease. The blood leukocyte count decreased until 6h after the injection in the both sublethal and lethal groups, but there was no significant difference between the two groups. The lung weight difference of the lethal group was significantly higher than that in the control group 12h after injection (p less than 0.05). Therefore, the elevated blood TNF activities in our study may be not elicited from alveolar macrophages but mainly from liver and spleen macrophages. There may be a relationship between the lung edema and the elevated blood TNF activity in the lethal groups.

Animals↗

PubMed1991

Direct measurement of intracellular free calcium in cultured human puerperal myometrial cells stimulated by oxytocin: effects of extracellular calcium and calcium channel blockers.

The changes in intracellular free calcium concentration ([Ca2+]i) induced by oxytocin in single cells of cultured human puerperal myometrium were measured with the calcium-sensitive fluorescent dye fura 2 in a digital imaging fluorescence microscopic system. Oxytocin at concentrations of 30-300 nmol/L induced a dose-dependent increase in [Ca2+]i with a peak at 20 seconds. This increase depended mainly on extracellular calcium ([Ca2+]ex) at concentrations of 0.6-4.8 mmol/L. In the absence of [Ca2+]ex, the increase was only 16% of that in its presence. The voltage-sensitive calcium channel blockers nicardipine, nifedipine, and nitrendipine had similar effects, causing significant suppression of the increase in [Ca2+]i induced by oxytocin. Diltiazem also suppressed the increase in [Ca2+]i, though less than the other calcium channel blockers. These data indicate that the increase in [Ca2+]i induced by oxytocin is predominantly dependent upon [Ca2+]ex. Furthermore, the data explain why calcium channel blockers are effective for weakening uterine muscle contractions and indicate which type of blocker is most effective.

Calcium↗

PubMed1990

Superoxide anion increases intracellular free calcium in human myometrial cells.

We investigated the effects of superoxide anion on the intracellular free calcium concentration ([Ca2+]i) in human cultured myometrial cells using a calcium-sensitive fluorescent dye, indo-1, and a digital imaging fluorescence microscopic system. Hypoxanthine (HX) plus xanthine oxidase induced a rise in [Ca2+]i in a manner dose-dependent on xanthine oxidase. The increase in [Ca2+]i in the absence of extracellular calcium ([Ca2+]ex) was 10% of that in the presence of [Ca2+]ex. Nifedipine, which blocks voltage-sensitive calcium channels, also reduced the increase in [Ca2+]i induced by HX-xanthine oxidase. Superoxide dismutase or superoxide dismutase plus catalase, which metabolizes superoxide anion, inhibited the effect of HX-xanthine oxidase on [Ca2+]i. The desensitization of the effect of superoxide anion on [Ca2+]i was investigated by pulsatile administration of HX and xanthine oxidase. Desensitization was observed on pulsatile administration of HX-xanthine oxidase at 2-min intervals. These data suggest that superoxide production may participate in uterine contraction via [Ca2+]i increase.

Calcium↗

PubMed1990

Vasodilator effects of sarafotoxins and endothelin-1 in spontaneously hypertensive rats and rat isolated perfused mesentery.

Sarafotoxins (SRTa, SRTb and SRTc) and ET-1 produced a potent vasodilator effect in spontaneously hypertensive rats in vivo and in rat isolated perfused mesenteries in vitro. Among these peptides SRTc demonstrated the most potent vasodilator activity, and was three times more active than SRTa in both preparations. These peptides induced endothelium-dependent vasodilatation in vitro and pretreatment with methylene blue inhibited this effect, while exposure to the antagonists of other vasodilators did not. In contrast, [nitrophenylsulfenylated Trp21]SRTc, SRTc(1-18) and reduced and S-carboxymethylated SRTc caused no vasodilatation in either animal model; the vasodilator effect of acetylated SRTc was less potent than that of SRTc. These results suggest that (i) the vasodilatations of these peptides may be exerted through the release of endothelium derived relaxing factor; (ii) the C-terminal Trp21 and disulfide bonds are essential; and (iii) the N-terminal amino group plays an important role in vasodilator activity.

Amino Acid Sequence↗

PubMed1990

Structure-activity relationship in vasoconstrictor effects of sarafotoxins and endothelin-1.

Sarafotoxins (SRTa, SRTb and SRTc) as well as endothelin-1 (ET-1) produced vasoconstrictions in rat thoracic aorta, rat isolated perfused mesentery and pithed rat in various of extents. The potency was ET-1 greater than SRTb greater than SRTa greater than SRTc at lower doses, but SRTb greater than ET-1 greater than SRTa greater than SRTc at higher doses. [Nitrophenylsulfenylated Trp21]SRTb and SRTb(1-19) caused no vasoconstriction. Either the reduction and carboxymethylation of Cys residues, the destruction of the intramolecular loop or the production of the non-natural disulfide bond, eliminated the constrictor activity. These results indicate that Trp21 and the intramolecular loop structure are essential, and Lys9 and Tyr13 may play some important roles for the vasoconstrictor activity of these peptides.

Animals↗