Biomedical subjects

K Tasaka

Publications and source records attributed to K Tasaka.

At least 199 records · Page 11Linked to original sources

PubMed1988

Biphasic activation of cytosolic free calcium and LH responses by gonadotropin-releasing hormone.

Gonadotropin-releasing hormone (GnRH) stimulates rapid peak increases in [Ca2+]i and LH release, followed by lower but sustained elevations of both [Ca2+]i and hormone secretion. Omission of extracellular Ca2+ only slightly decreased the peak of [Ca2+]i, but reduced the peak LH response by 40% and prevented the prolonged increases in [Ca2+]i and LH release. Dihydropyridine calcium antagonists did not affect the peak [Ca2+]i and LH responses, but reduced the sustained increases by up to 50%. Whereas GnRH-induced mobilization of intracellular calcium initiates the LH peak, and Ca2+ entry through dihydropyridine-insensitive channels contributes to the peak and plateau phases of LH release, dihydropyridine-sensitive L-type Ca2+ channels participate only in the sustained phase of gonadotropin secretion.

Animals↗

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

The influence of histamine on precursors of granulocytic leukocytes in murine bone marrow.

The effect of histamine on granulocytic progenitor cells in murine bone marrow was studied in vitro. When bone marrow cells were cultured for three days with the drug, 10(-8) M to 10(-5) M of histamine stimulated differentiation and proliferation of myeloid precursor cells. Subsequently, the number of descendant cells, such as metamyelocytes and neutrophils, increased dose-dependently. Co-existence of equimolar H2 blockers such as cimetidine and ranitidine completely suppressed this effect of histamine, though this was not the case with an H1 blocker/histamine combination. Significant increase in 3H-thymidine incorporation was observed almost exclusively in myeloblasts, promyelocytes and myelocytes after exposure to histamine at concentrations higher than 10(-8) M. Also, selective incorporation of 3H-histamine into bone marrow cells was observed in myeloblasts and promyelocytes, but histamine incorporation was not influenced by the presence of either of histamine agonists or antagonists. While histamine, via H2 receptors, selectively increased the number of granulocytic colony forming units in culture (CFU-C), it had no such effect on macrophage colonies. Considering these findings, it was concluded that histamine promotes proliferation and differentiation of granulocytic myeloid cells via 1) H2 receptors in the CFU-C stage and 2) histamine receptors which are neither H1 nor H2 in the stages of myeloblast and promyelocyte differentiation.

Animals↗

PubMed1988

The effects of H1- and H2-receptor blocking agents on postsynaptic potentials recorded from the bull-frog sympathetic ganglion.

The effects of H1-blockers (pyrilamine, diphenhydramine and promethazine) and H2-blockers (cimetidine, ranitidine) on the postsynaptic potentials of the bull-frog sympathetic ganglion were studied by means of the sucrose gap method. All the H1-blockers tested, at concentrations of 10(-6)-10(-4) M, depressed the amplitudes of both action and slow postsynaptic potentials in positive and negative directions in a concentration-dependent manner; these drugs had more potent inhibitory effects on postsynaptic potentials. In the case of H2-blockers, action and postsynaptic potentials were slightly depressed as perfusion continued at 10(-4) M. From the present experiments, it was concluded that H1-blockers directly inhibit postsynaptic potentials of the sympathetic ganglions, and that this inhibition may be responsible for various autonomic disturbances attributed to H1-blockers.

Action Potentials↗

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↗

PubMed1988

Vasoactive intestinal peptide stimulates gonadotropin-releasing hormone release from rat hypothalamus in vitro.

The effects of vasoactive intestinal peptide (VIP) on the releases of LH and GnRH were examined in a sequential double chamber perifusion system by perfusing the medio-basal hypothalamus and/or pituitary excised from normal female rats in diestrus or ovariectomized rats. When the medio-basal hypothalamus and pituitary from normal rats in series were perifused with VIP (10(-6) mol/l), the concentration of LH in the efflux was increased by 59-181% above that before the injection (P less than 0.05), VIP having a dose-dependent effect. VIP had no effect on LH release from the pituitary perifused alone. Infusion of VIP at 10(-6) mol/l induced a significant release (84-159% increase, P less than 0.05) of GnRH from the medio-basal hypothalamus. Infusion of 10(-6) mol/l VIP induced a significant release (41-99% increase, P less than 0.05) of LH in ovariectomized rats. These findings suggest that VIP induces GnRH release from the medio-basal hypothalamus, resulting in LH release from the pituitary, and that this process does not require ovarian estrogen.

Animals↗

PubMed1988

Analysis of bronchomotor tone in anesthetized guinea pigs by impedance plethysmography: a simple method for the evaluation of bronchodilator action.

The transthoracic impedance method for measurement of bronchomotor tone was studied in anesthetized guinea pigs. Impedance change (delta Z) recorded from the 2nd to the 6th rib level increased linearly in accordance with the increment of inspirated volume (delta V); the maximum ratio of delta Z to delta V with the least cardiac artifact was measured at the level of the 6th rib. Histamine (5 micrograms/kg, i.v.) caused an increase in intratracheal pressure and a decrease in delta Z in guinea pigs. The fact that the delta Z peak lagged behind that of intratracheal pressure indicated that air flow movement was disturbed at the restricted bronchioles. In anesthetized dogs, the waveform of DC-impedance was similar to that of both flow volume and intraesophageal pressure. The waveform of AC-impedance, the signals of which are differentiated from DC-impedance, was similar to that of the flow rate. Following histamine administration (10 micrograms/kg, i.v.), the flow rate amplitude increased during inspiration and decreased during expiration. In passively immunized guinea pigs, antigen challenge induced a rapid increase in intratracheal pressure and a concomitant decrease in the amplitude of AC -impedance. Pretreatment with fenoterol (5-20 micrograms/kg, i.v.) inhibited these changes dose-dependently. It was concluded that delta Z measurement is a beneficial method for investigating respiratory dynamics in guinea pigs and is especially useful for evaluating the efficacy of bronchodilating action of test compounds.

Anesthesia↗

PubMed1987

The effects of cephem antibiotics and related compounds on the aldehyde dehydrogenase in rat liver mitochondria.

The effects of cephem antibiotics and their related compounds on aldehyde dehydrogenase obtained from rat liver mitochondria were studied. A pH of 8.8 and reaction temperature 24 degrees were the conditions for measurement of enzyme activity. The apparent Michaelis constant Km values for NAD, acetaldehyde and propionaldehyde were 3.8 X 10(-5) M, 4.0 X 10(-5) M and 2.5 X 10(-5) M, respectively. Cefamandole, cefoperazone and cefmetazole, having a 1-methyl-5-thiotetrazol group at position 3 of the cephem ring, caused a relatively potent inhibition of aldehyde dehydrogenase. Cefmetazole and cefoperazone also showed a significant inhibition on highly purified yeast aldehyde dehydrogenase; the extent of inhibition on yeast enzyme was almost the same as that on rat mitochondrial aldehyde dehydrogenase. The decrease in enzyme activity effected by 1-methyl-1H-tetrazol-5-thiol (MTT) was greater than those of 1H-tetrazol (TZ), 1H-tetrazol-5-thiol and 1-(2-dimethylaminoethyl)-1H-tetrazol-5-thiol, but was, of course, less than that of disulfiram. Cefamandole, cefmetazole and MTT showed competitive inhibition with NAD, while TZ was uncompetitive inhibitor with respect to both NAD and acetaldehyde. Enzyme inhibition caused by disulfiram, cefmetazole and MTT increased time-dependently and the addition of 2-mercaptoethanol into the medium effectively and completely restored enzyme inhibition. These results suggest that thiol group at position 5 of 1H-tetrazol ring is responsible for the type of inhibition with NAD, and methyl group at position 1 of 1H-tetrazol ring is important to exhibit a potent inhibition on aldehyde dehydrogenase.

Aldehyde Dehydrogenase↗

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

The relationship between incorporation of histamine and differentiation of neutrophil progenitors in murine bone marrow.

Histamine, at concentrations higher than 10(-8) M, promoted the differentiation of myeloblasts and promyelocytes of murine bone marrow. This effect was not inhibited by the presence of either pyrilamine or cimetidine. Incorporation was highly specific to histamine without being affected by various H1- and H2-agonists or antagonists, and seemed to be mediated by a specific transport system which includes new protein synthesis and is generated after the addition of 3H-histamine.

Animals↗

PubMed1987

Immunological studies on delayed hypersensitivity to phenytoin--I. A new method for preparing phenytoin antiserum.

The present study was initiated to produce an antiserum to phenytoin with high specificity and sensitivity which would be suitable not only for determination of blood phenytoin concentration but also for induction of a hypersensitivity reaction to phenytoin in experimental animals. p-Aminophenytoin was synthesized and identified by means of IR, 1H-NMR and mass spectroscopy. BSA-phenytoin conjugate was prepared by using p-aminophenytoin, BSA and, as a coupling reagent, glutaraldehyde. Satisfactory response to immunization was achieved at a 9.8:1 molar ratio of p-aminophenytoin to BSA. The antiserum obtained from rabbits immunized with BSA-phenytoin conjugate exhibited practically no cross-reactivity with either phenytoin metabolites or other anti-epileptic drugs, indicating that this antiserum provides sufficiently high specificity. In our experiments, the lower limit for detecting phenytoin was 2 ng using RIA, whereas 200 ng was the minimum amount detectable by HPLC. Thus, by a difference of two orders of magnitude, the present RIA method shows a much higher sensitivity than that of HPLC, though we found a good correlation of simultaneous determinations of serum phenytoin between the two methods. Reproducibility of phenytoin determination in plasma was confirmed by calculating the coefficient of variance. The values were less than 10%.

Animals↗

PubMed1987

Involvement of H1 histamine receptor in basal and estrogen-stimulated luteinizing hormone-releasing hormone secretion in rats in vitro.

For determination of the roles of histamine and its receptors, H1 and H2, in the control of basal and estrogen-induced LH-RH secretion, the mediobasal hypothalamus (MBH) and/or pituitary was excised from normally cycling female rats and perifused in an in vitro sequential double chamber perifusion system. Administration of 10(-7) M histamine caused significant release (90-170% increase, p less than 0.05) of LH from the pituitary in sequence with the MBH, whereas 10(-7) M histamine had no effect on LH release from the pituitary perifused alone; administration of 10(-5) M 2-methylhistamine, an H1 agonist, induced significant release (50-120% increase, p less than 0.05) of LH-RH from the MBH, and addition of 10(-5) M mepyramine, and H1 antagonist, abolished this LH-RH release. The LH concentrations in the efflux were not affected by the administration of the H2 agonist 4-methylhistamine. Estradiol caused significant release of LH-RH from the MBH and LH from the pituitary in sequence with the MBH. The estradiol-induced release of LH-RH and LH were completely abolished by perifusion with medium containing 10(-5) M mepyramine. The H2 receptor antagonist ranitidine did not affect estradiol-induced LH release. Histamine did not change the LH release induced by 20 ng LH-RH. These findings suggest that histamine induces release of hypothalamic LH-RH, and that histamine H1 receptors in the hypothalamus are involved in the basal and estradiol-induced LH-RH release.

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

Substance P stimulates gonadotropin-releasing hormone release from rat hypothalamus in vitro with involvement of oestrogen.

The effects of substance P on the release of LH and GnRH were examined in a sequential double-chamber perifusion system by perfusing the medio-basal hypothalamus and/or pituitary excised from normal female rats in dioestrus or ovariectomized rats. When the medio-basal hypothalamus and pituitary from normal rats were perifused in series with substance P (10(-6) mol/l), the concentration of LH in the efflux was significantly (P less than 0.05) increased by 70-120% compared with that before the injection, but substance P had no effect on LH release from the pituitary perifused alone. This LH release by substance P increased in a dose-dependent manner and was blocked by substance P antagonist. Administration of 10(-6) mol/l substance P induced a significant release (40-80% increase, P less than 0.05) of GnRH from the medio-basal hypothalamus. Infusion of 10(-6) mol/l substance P induced significant release (50-100% increase, P less than 0.05) of LH and GnRH in ovariectomized rats with an implanted oestradiol capsule, but caused no significant increase in LH release in ovariectomized rats without an oestradiol capsule. Progesterone injection to both ovariectomized rats and ovariectomized rats with an implanted oestradiol capsule had no significant effect on the response of LH to substance P. These findings suggest that substance P induces GnRH release from the medio-basal hypothalamus, resulting in LH release from the pituitary, and that oestrogen may be involved in these processes.

Animals↗

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↗

PubMed1987

Effects of antihistamines on the spinal reflex in rats.

The effect of antihistamines on the spinal reflex in rats was studied. When H1-blocking agents such as pyrilamine, promethazine and diphenhydramine were given intravenously, both monosynaptic reflex (MSR) and polysynaptic reflex potentials (PSR) were inhibited in a dose-dependent fashion without affecting the dorsal root reflex and dorsal root-dorsal root potential. The extent of suppression of the MSR and PSR measured in spinal rats was smaller than that of intact rats. When H1-blocking agents (0.25-5.0 nmol) were applied by intraspinal microinjection close to the motoneuron, the MSR and PSR were depressed dose-dependently. Simultaneous application of carbachol partially blocked the inhibitory effects of H1-blocking agents induced by intraspinal microinjection. Also, the motoneuron discharges evoked by microinjection of glutamic acid or acetylcholine were depressed by simultaneous administration of any of H1-blocking agents tested. However, H2-blocking agents, such as cimetidine and ranitidine, given either intravenously or intraspinally had a scarcely measurable effect on the spinal reflex. The depression of H1-blocking agents on the spinal reflex is due to a direct inhibition of the motoneuron on the one hand. On the other hand, there is also an involvement of higher centers in the central nervous system increasing potential depression.

Animals↗

PubMed1987

[UFT therapy of experimental gastric cancer in beagles induced by ENNG].

Therapeutic effects and dynamics of UFT were studied using beagles with ENNG-induced gastric cancers. Nine canine subjects confirmed to have gastric cancers by punch biopsy under gastrofiberscopy were divided into 3 group given 5 mg/kg/day of UFT for 101 days, 7.5 mg/kg/day for 67 days and 12 mg/kg/day for 45 days, respectively. Although the extent of macroscopic change revealed by gastrofiberscopy was minor, one of the dogs in the third group did show a Grade II b effect according to the criteria of Histopathological Effects on Cancer Tissues by Chemotherapy proposed by Oboshi and Shimozato. Animals were sacrificed by bleeding 4 hours after the last administration of anticancer agent and concentration of 5-FU and tegafur in the serum and each organ were determined. It was recognized that the concentration of anticancer agent in gastric cancer tissue was higher than that in neighboring normal gastric tissue.

Animals↗