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Biomedical subjects

K Tasaka

Publications and source records attributed to K Tasaka.

At least 217 records · Page 12Linked to original sources
PubMed1987

Antihypertensive effects of nisoldipine and reference drugs in certain types of hypertensive rats.

The hypotensive effects of nisoldipine (Bay K 5552), compared with those of nifedipine, nicardipine and hydralazine, in normotensive rats (NR), spontaneously hypertensive rats (SHR), DOCA-NaCl hypertensive rats (DNR) and renal hypertensive rats (RHR), were studied. The changes in plasma renin activity (PRA) after treatment with nisoldipine and these reference drugs were also studied. The results of this study revealed that: 1. Nisoldipine caused more potent antihypertensive effects in SHR, DNR and RHR than in NR. 2. The antihypertensive effects of nisoldipine in SHR were almost equipotent to those of nifedipine, nicardipine and hydralazine. However, in NR, DNR and RHR, the effects of nisoldipine were weaker than those of the reference drugs. 3. The positive chronotropic effects of nisoldipine were less remarkable than those elicited by nifedipine, nicardipine and hydralazine in all types of hypertensive rats, except SHR. 4. As did nifedipine and nicardipine, nisoldipine caused an increase of the plasma renin activity in NR and SHR, though its potency was weaker than those of nifedipine and nicardipine.

Animals↗
PubMed1986

Participation of voltage-dependent calcium channels in the action of gonadotropin-releasing hormone.

The roles of calcium ions and voltage-sensitive calcium channels in gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release were investigated in rat anterior pituitary cells. The calcium ionophores A23187 and ionomycin stimulated LH release from cultured pituitary cells, in which ionomycin (5 X 10(-5) M) was as effective as a maximal concentration of GnRH (10(-8) M). In addition, a concentration of the calcium channel agonist methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine- 5-carboxylate (BK 8644) (10(-8) M), which did not alter basal LH release, potentiated the ability of submaximal (10(-10) and 10(-9) M) doses of GnRH to increase LH secretion. Furthermore, concentrations of the calcium channel antagonist nitrendipine (10(-8)-10(-5) M) that did not alter basal LH release, inhibited GnRH-stimulated LH secretion by 30-40%. Nitrendipine (10(-8) M) also blocked the potentiation of GnRH-induced LH secretion by BK 8644. During column perifusion of pituitary cells, 10(-8) M nitrendipine reduced the LH response to a 2-min pulse of 10(-8) M GnRH by about 40%. In Quin-2-loaded pituitary cells, supramaximal doses (10(-6) M) of a potent GnRH agonist rapidly elevated cytoplasmic Ca2+ by 50-100 nM. Concomitant treatment with nitrendipine decreased the GnRH agonist-induced Ca2+ signal by 40-60%. These results indicate that increases in intracellular Ca2+ via voltage-sensitive calcium channels partially reproduce GnRH action, and also that GnRH causes activation of such channels. However, the increase in cytoplasmic Ca2+ concentration during GnRH action must originate in part from mobilization of internal Ca2+ stores, and its relatively small magnitude may be consistent with the concomitant activation of protein kinase C as an intermediate step in GnRH action.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Distribution of actin filaments in rat mast cells and its role in histamine release.

The distribution of actin filaments was confirmed by immunofluorescence microscopy and immuno-electron microscopy in nonsecreting and secreting rat peritoneal mast cells. In a resting cell, immunofluorescence of the actin showed up as a net-like formation surrounding each granule. After stimulation with compound 48/80 or A-23187, the distribution of the actin filaments became very irregular and disordered, disappearing completely in some areas within the cell and expanding in conjunction with the swelling of the granules. Similar changes are seen in a passively sensitized mast cell exposed to antigen. When cells were pretreated with cytochalasin B or colchicine, the distribution of actin filaments was not greatly affected by stimulation. The results clearly show that actin filaments exist in mast cells.

Actins↗
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

Effect of histamine on delayed-type hypersensitivity in mice.

The effect of histamine on delayed-type hypersensitivity provoked in the abdominal cavity of mice was studied. When histamine (0.1-10 mg/kg) was injected twice a day for 2 consecutive days after antigen challenge, cell accumulation in the inflamed site and the production of lymphokine was significantly suppressed. Similar suppressive effects were observed after injection with an H2-agonist, dimaprit, but not in the case of an H1-agonist, 2-methylhistamine. The effect of histamine on cell accumulation in an implanted sponge was blocked by the H2-antagonists, cimetidine and ranitidine, but only slightly by the H1-antagonists, pyrilamine and diphenhydramine. In adrenalectomized mice, the suppressive effect of histamine was slightly weaker than in normal mice, but the inhibitory effect of histamine was almost completely blocked by H2-antagonists in both cases. The suppressive effect of histamine on the production of lymphokine (macrophage chemotactic factor) was also blocked by cimetidine. Using gel chromatography, the chemotactic activity fraction was eluted as molecules having a molecular weight of 30,000-70,000. These results suggest that the histamine-induced suppression of the delayed-type hypersensitivity reaction in mice is affected mainly by the production of lymphokine(s) via an H2-receptor-bearing lymphocyte.

Adrenalectomy↗
PubMed1986

Effects of various cephem antibiotics on ethanol metabolism and their structure-activity relations.

The effects of various cephem antibiotics and related compounds on ethanol metabolism were studied in association with their chemical structures. In rats, cefoperazone, cefbuperazone, cefamandole, latamoxef, cefmetazole, cefotetan, cefmenoxime and cefminox which have the [(1-methyl-1H-tetrazol-5-yl) thio] methyl group at position 3 of the cephem ring caused a significant increase in the blood acetaldehyde concentration. In the last three compounds, disulfiram-like activity was less potent than that evaluated in the preceding compounds. Cefazolin and ceftezole having a 1H-tetrazol group at position 7 also showed a disulfiram-like activity. A single administration of 1H-tetrazol also increased the blood acetaldehyde concentration. Both blood ethanol and acetaldehyde values were increased significantly on administration of these drugs. In beagle dogs, cefoperazone induced a less remarkable but much more sustained increase in the blood acetaldehyde. These results indicate that the 1H-tetrazol group, as well as the [(1-methyl-1H-tetrazol-5-yl) thio] methyl group, is responsible for inducing a disulfiram-like action and that there is a difference in the potency of the disulfiram-like activity among the drugs having a [(1-methyl-1H-tetrazol-5-yl)thio] methyl group at position 3 of the cephem ring in relation to those in which the side chain is substituted at position 7.

Acetaldehyde↗
PubMed1986

Wen-jing-tang, a traditional Chinese herbal medicine increases luteinizing hormone release in vitro.

For examination of the effect on luteinizing hormone (LH) release of Wen-Jing-Tang, a traditional Chinese herbal medicine, the pituitary from normal female rats in diestrus was perifused alone or in sequence with the mediobasal hypothalamus (MBH) in a sequential double-chamber perifusion system. Wen-Jing-Tang at 5 or 500 micrograms/ml induced significant LH release (60-95% increase) from the pituitary in series with the MBH, but had no effect on LH release from the pituitary perifused alone. These data suggest that Wen-Jing-Tang induces LH release from the pituitary through hypothalamic LH-RH.

Animals↗
PubMed1986

Influence of histamine and related compounds on the hypnotic effect of thiopental in mice.

Intraventricular injection of histamine (Hi) significantly prolonged thiopental sleeping time at doses of 0.5 microgram or larger. Both 1-methylHi and imidazole-4-acetic acid, however, did not affect thiopental narcosis. Pretreatment with alpha-fluoromethylhistidine diminished the effect of Hi, while histidine, metoprine and quinacrine prolonged thiopental narcosis. Injection with 2-methylHi did not affect thiopental sleeping time, while as in the case of Hi, 4-methylHi augmented the thiopental effect. In addition, H2-receptor blocking agents such as cimetidine, ranitidine and famotidine clearly antagonized Hi-induced prolongation of thiopental narcosis, while pyrilamine and chlorpheniramine had no effect. These results indicate that Hi-induced prolongation of thiopental narcosis appears to be exerted via H2-receptors and is, in some way, related to the Hi content in the brain.

Animals↗
PubMed1986

Hydatidiform mole in a triplet pregnancy following gonadotropin therapy.

A first case is reported of complete hydatidiform mole with two coexistent fetuses in a triple pregnancy following human menopausal gonadotropin human chorionic gonadotropin (hMG-hCG) therapy. The molar mass and two fetuses were delivered separately at 17 weeks of gestation. The fetuses were female (155 g) and male (160 g) with individual placentae (85 g, 90 g). The hydatidiform mole (650 g) had a normal 46,XX karyotype. The sexes of the two fetuses and the karyotype of the mole are consistent with previous reports that the chromosomes of fetuses and moles are derived from both parents and the father, respectively.

Adult↗
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↗
PubMed1986

Comparative study of various H1-blockers on neuropharmacological and behavioral effects including 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole difumarate (KB-2413), a new antiallergic agent.

In a conditioned avoidance response tested in rats, all of the H1-blockers employed caused a dose-related inhibition at doses 5-20 mg/kg (i.v.) except for ketotifen that elicited significant suppression even at a dose of 1 mg/kg. No inhibition was seen after administration of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole difumarate (KB-2413). ED50s were ranged from 4.1 to 7.4 mg/kg in diphenhydramine, pyrilamine and promethazine. In laminectomized rats, diphenhydramine, pyrilamine, promethazine and ketotifen suppressed the amplitudes of monosynaptic reflex potentials at doses higher than 2 mg/kg (i.v.). In the case of chlorpheniramine, significant inhibition was observed at a dose of 20 mg/kg. In a polysynaptic reflex, similar but less prominent inhibitions were affected by those drugs. However, KB-2413 did not influence spinal reflexes even at a dose of 20 mg/kg. In the rat phrenic nerve-diaphragm preparation, perfusion of H1-blockers at a concentration of 10(-5) M decreased the amplitudes of end-plate potentials except for chlorpheniramine and KB-2413. At 10(-4) M, all the test drugs caused significant inhibition. When the action potential of superior cervical ganglion was measured by the sucrose gap method, promethazine inhibited the action potential significantly at 10(-6) M, but the rest of the test drugs depressed the potentials at 10(-5) M. In spontaneous EEG, all H1-blockers caused a marked drowsy pattern at lower doses (2-5 mg/kg) except for chlorpheniramine, while in higher doses (10-20 mg/kg) epileptic signs in EEG with or without convulsive behavior were noticed. However, after KB-2413 (5-20 mg/kg) neither drowsy nor seizure pattern was observed, in EEG or behavior.

Action Potentials↗
PubMed1986

Pharmacological profiles of 2-carboxyphenyl-1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetate and 2-[(2-carboxyphenoxy)-carbonyl]phenyl-1-(4-chlorobenzoyl)-5-meth oxy-2- methylindole-3-acetate, new antiinflammatory agents.

When the effects of new antiinflammatory drugs, 2-carboxyphenyl-1-(4-chlorobenzoyl)-5-methoxy-2-methyl-indole-3-acetate (TB 219) and 2-[(2-carboxyphenoxy)carbonyl]phenyl-1-(4-chlorobenzoyl)-5- methoxy-2-methylindole-3-acetate (TB 220), were investigated in various experiments, the following results were obtained: 1. TB 219 and TB 220 showed remarkable inhibitory effects on carrageenin edema, ultraviolet erythema and adjuvant arthritis. Although TB 219 displayed almost equipotent or slightly more potent effect than those of indometacin and acemetacin, TB 220 was slightly less effective than these two reference drugs except for the therapeutic effect on adjuvant arthritis. 2. TB 219 and TB 220 inhibited the writhing syndrome induced by acetic acid and inflammatory hyperesthesia, and they provided a significant antipyretic activity. 3. Both drugs elicited almost negligible side effects in the gastrointestinal tract even after the repeated administrations. Especially, ulcerogenic activity of TB 220 was extremely weak. LD50's of both drugs are higher than that of indometacin in rats. 4. Both drugs elicited no appreciable changes in general behavior in mice and rats after oral administration. After intraperitoneal or intravenous injection of these two drugs, no marked changes in spontaneous EEG pattern and the spinal reflex were observed.

Animals↗
PubMed1985

The effects of histamine and some related compounds on conditioned avoidance response in rats.

When histamine (Hi) and other agonists were applied intraventricularly, Hi caused a dose-dependent inhibition of the avoidance response in rats; its ED50 was 3.60 micrograms. 1-methylHi, 1-methylimidazole acetic acid and imidazole acetic acid which are major metabolites of Hi produced no inhibitory effect even at 50 micrograms. H1-agonists (2-methylHi and 2-thiazolylethylamine) also depressed the avoidance response; their dose-response lines run parallel to that of Hi. The depressant effects of H2-agonists (4-methylHi and dimaprit) were relatively weak; their dose-response lines were not parallel to that of Hi. When antagonists were pretreated intravenously, Hi action was clearly antagonized by diphehydramine and pyrilamine, but not by cimetidine or ranitidine. Intraventricular injection of Hi mixed with cimetidine or ranitidine did not change the effect induced by Hi alone. The avoidance response was not affected by noradrenaline, dopamine or 5-hydroxytryptamine. Although acetylcholine (ACh) suppressed the avoidance response dose-dependently, its effect was much weaker than that of Hi. Pretreatment with cholinergic blocking drugs (atropine and scopolamine) antagonized ACh action but not Hi action. From these results, it is assumed that the inhibitory effect of Hi on the avoidance response is preferentially linked to the H1-receptor. After intraventricular application of 3H-Hi, the highest radioactivity was determined in the hypothalamus.

Acetylcholine↗
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↗
PubMed1985

A new method of eliciting delayed hypersensitivity in the mouse abdominal cavity.

A new method of determining delayed hypersensitivity quantitatively was investigated in mice. Mice were sensitized with 150 micrograms of ferritin and, 3 weeks later, antigen challenge was performed by implanting a sponge containing antigen in the abdominal cavity. Cells accumulated in the sponge markedly increased in number for 24-72 h after the challenge; mononuclear cells predominated by 48 h. When sensitized lymphocytes were transferred passively to a normal recipient, marked cell accumulation in the sponge was found 48 h after the challenge. Immunological specificity was confirmed in animals sensitized to antigen and receiving passive transfer of sensitized cells. Strain differences in this reaction were observed. Cortisone (20 mg/kg for 6 days before challenge) significantly decreased cell accumulation. Delayed hypersensitivity was also elicited in the ear of sensitized animals. Extracts of sponges removed from antigen-challenged mice had macrophage chemotactic activity.

Animals↗
PubMed1985

Inhibitory effect of lysophosphatidylcholine on the histamine release from rat peritoneal mast cells.

Histamine release from isolated rat peritoneal mast cells induced by compound 48/80 (0.5 microgram/ml) or antigen-antibody reaction was inhibited by lysophosphatidylcholine in a dose-dependent fashion at concentrations up to 4 microM. Within the same range of concentration, lysophosphatidylcholine exhibited a membrane-stabilizing action on the model membrane systems decreasing the permeability of lipid bilayer and the fluidity of liposomal membrane in the liquid crystalline state. At concentrations higher than 8 microM, lysophosphatidylcholine damaged the cell membrane and subsequently histamine was released. It was assumed that lysophosphatidylcholine may act as an endogenous membrane stabilizer inhibiting histamine release in normal mast cells.

Animals↗
PubMed1985

Dopamine decreases release of luteinizing hormone releasing hormone from superfused rat mediobasal hypothalamus.

The effects of dopamine hydrochloride (DA) on the releases of LHRH and LH were examined in a serial sequential double chamber perifusion system by perifusing the mediobasal hypothalamus including the preoptic area and/or pituitaries excised from diestrus female rats. DA, perifused at a dose of 4.2 X 10(-4) M, significantly (p less than 0.05) lowered LH secretion from the pituitary in series with the hypothalamus 40-80% below the preinfusion level, but it had no effect on LH efflux from the pituitary perifused alone. DA also significantly (p less than 0.05) reduced the LHRH level 20-40% below the initial level. Perifusion with the DA receptor blocker haloperidol at a concentration of 10(-6) M abolished the suppressive effect of DA on LH secretion. These findings indicate that DA suppressed hypothalamic LHRH release, resulting in decrease in LH secretion from the pituitary in diestrus rats.

Animals↗