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Biomedical subjects

K Ohuchi

Publications and source records attributed to K Ohuchi.

161 records · Page 9Linked to original sources
PubMed1980

Comparative study between steroidal and nonsteroidal anti-inflammatory drugs on the mode of their actions on vascular permeability in rat carrageenin-air-pouch inflammation.

In an attempt to clarify mechanisms of anti-inflammatory actions of steroidal and nonsteroidal anti-inflammatory drugs with special reference to the possible role of E type prostaglandins in the inflammatory process, mode of actions of these drugs was investigated by using acute exudative stage and chronic proliferative stage of carrageenin-air-pouch inflammation in rats. This inflammation was induced on the back of rats by subcutaneous injection with air and carrageenin solution. Plasma exudation in the inflammation locus was determined with the aid of radioiodinated serum albumin. In the acute exudative stage of this inflammation, a single oral administration of dexamethasone, indomethacin, phenylbutazone or aspirin all exerted potent anti-exudative effect, while in the chronic proliferative stage, only dexamethasone was effective in inhibiting the exudation of the labeled albumin. Prostaglandin E level in the exudate of the acute stage inflammation was suppressed by either dexamethasone or indomethacin in accordance with the inhibition of the vascular permeability. These results suggest (1) significant role of prostaglandin E in the acute exudative inflammation, (2) similarity between steroidal and nonsteroidal anti-inflammatory drugs in the mechanism of their anti-exudative actions in the acute inflammation, (3) independency of the exudative process in the chronic proliferative inflammation from prostaglandins and (4) role of extra-prostaglandin mechanism(s) for the anti-exudative action of the anti-inflammatory steroids.

Animals↗
PubMed1979

Prostaglandins E2, F2 alpha, 6-keto-F1 alpha and thromboxane B2 levels in carrageenin-induced inflammatory exudates in the rat air-pouch granuloma.

Levels of PGE2, PGF2 alpha, PGI2 (measured as 6-keto-PGF1 alpha), and thromboxane B2 were determined in rat inflammatory excuates induced 1, 3, and 7 days after carrageenin injection into air-pouch granuloma. The PGE2 and 6-keto-PGF1 alpha levels found in the exudate could not account for the differences in PGE2-like activity as measured by biologic and serologic methods.

6-Ketoprostaglandin F1 alpha↗
PubMed1978

Stimulation of prostaglandin synthesis by tumor-promoting phorbol-12, 13-diesters in canine kidney (MDCK) cells. Cycloheximide inhibits the stimulated prostaglandin synthesis, deacylation of lipids, and morphological changes.

Tumor-promoting 12-O-tetradecanoyl-phorbol-13-acetate and phorbol-12, 13-di-decanoate, but not the non-tumor-promoting 4alpha-phorbol-12, 13-di-decanoate, stimulated deacylation of cellular lipids, prostaglandin biosynthesis, and morphological changes in cultured MDCK cells. The increased prostaglandin biosynthesis and morphological changes required at least 24 h for expression. Cycloheximide inhibited the stimulated prostaglandin biosynthesis, the changes in morphology, and the increased lipid deacylation, but hydrocortisone (1.0 microgram/ml) did not. Indomethacin (0.5 microgram/ml) completely inhibited the stimulated prostaglandin biosynthesis and also inhibited some deacylation of cellular lipids. Indomethacin, however, did not effect the 12-O-tetradecanoyl-phorbol-13-acetate-stimulated changes in morphology.

Cell Line↗
PubMed1978

Tumor promoting phorbol diesters stimulate release of radioactivity from [3H]-arachidonic acid labeled- but not [14C]linoleic acid labeled-cells. Indomethacin inhibits the stimulated release from [3H] arachidonate labeled cells.

The tumor promoting phorbol diester, 12-O-tetradecanoyl-phorbol-13-acetate, stimulates MDCK cells to deacylate cellular phospholipids and to produce prostaglandins when measured as the release of arachidonic acid and its metabolites into the culture fluid. Indomethacin, at levels of 2.8 x 10(-8) to 2.8 x 10(-6) M, inhibits the release of radioactivity from [3H]arachidonate labeled cells stimulated by 12-O-tetradecanoyl-phorbol-13-acetate treatment in a concentration dependent manner. At these concentrations, the conversion of released [3H]arachidonic acid into prostaglandins E2 and F2alpha and the production of PGE2 measured serologically also is suppressed in a concentration dependent manner. Indomethacin, at these levels, has no effect on the acylation of [3H]arachidonic acid into cellular lipids. The tumor promoting phorbol diester does not stimulate the release of radioactive materials from MDCK cells labeled with [14C]linoleic acid, although prostaglandin production by these cells is stimulated.

Animals↗
PubMed1978

Adriamycin stimulates canine kidney (MDCK) cells to deacylate cellular lipids and to produce prostaglandins.

Dog kidney (MDCK) cells treated with adriamycin (0.5 micrograms/ml) for 1 hr, produced from 2 to 7 times more prostaglandins E2 and F2alpha when measured in culture media 24, 48 and 72 hrs after the treatment. Indomethacin (ID50 less than 2 x 10(-8) M) and cycloheximide (0.5 micrograms/ml) inhibited this adriamycin-stimulated prostaglandin production. The aglycone of adriamycin (0.5 to 5.0 micrograms/ml) had little stimulating effect. Treatment of [3H]arachidonic acid-labeled MDCK cells with adriamycin (0.5 micrograms/ml) for 1 hr also stimulated deacylation of cellular lipids during subsequent incubation. Altered morphology of MDCK cells resulted from such treatment with adriamycin; indomethacin did not inhibit this change, but cycloheximide did.

Animals↗
PubMed1976

The content of prostaglandin E and prostaglandin F2alpha in the exudate of carrageenin granuloma of rats.

1. Granuloma was made by the subcutaneous injection of 2% carrageenin solution on the dorsum of male rats. Eight, 16, 24 and 72 h after the injection. the exudate from each rat granuloma was withdrawn and extracted for rpstaglandins. 2. Extracted prostaglandins were separated prostaglandin E and prostaglandin F group by silicic acid mini-column chromatography. Then the amount of prostaglandin E and prostaglandin F2alpha were determined by the radioimmunoassay method. 3. The levels of prostaglandin E in the granuloma exudates were 4.6 ng/ml at 8 h after the carrageenin injection, then decreased 3.6 ng/ml and to 1.1 ng/ml at 16 h and 24 h, respectively. Seventy-two h after the injection, prostaglandin E level was increased to 8.1 ng/ml. 4. The levels of prostaglandin F2alpha in the exudate were as follows: At 8 h after the carrageenin injection, the level was 9.4 ng/ml, then decreased to 1.3 ng/ml and to 0.8 ng/ml at 16 h and 24 h, respectively. Seventy-two h after the carrageenin injection, it was again elevated to 4.7 ng/ml. 5. The exudate of granuloma, 24 and 72 h after the carrageenin injection, was incubated with [3H]prostaglandin E1 at 37 degrees C for 30 min. Then the acidic ether extract was subjected to reversed phase partition chromatography. It was found that the exudate of 24 h and 72 h granuloma had little activity of prostaglandin 15alpha-hydroxy dehydrogenase.

Animals↗
PubMedDate not supplied

Suppression by adrenoceptor beta-agonists of vascular permeability increase and edema formation induced by arachidonate metabolites, platelet-activating factor, and tumor-promoting phorbol ester TPA.

Air-pouch-type inflammation was induced by injecting sodium carboxymethyl cellulose solution containing leukotriene C4 (LTC4, 3.20 x 10(-7) M, 0.2 micrograms/ml) and prostaglandin E2 (PGE2, 5.68 x 10(-6) M, 2.0 micrograms/ml), platelet-activating factor (PAF, 1 x 10(-6) M, 0.52 micrograms/ml), or 12-O-tetradecanoyl phorbol 13-acetate (TPA, 1.62 x 10(-6) M, 1.0 micrograms/ml) into an air pouch made on the dorsum of rats. Vascular permeability and tissue edema formation were significantly increased by injecting the phlogogen solution. The histamine level in the pouch fluid was dramatically increased by injecting TPA but not by LTC4 and PGE2, or PAF. Injection of isoproterenol or procaterol with the phlogogen solution produced dose-dependent suppression of both vascular permeability increase and tissue edema formation. However, the TPA-induced increase in the histamine level was not suppressed in parallel with the decrease of vascular permeability or tissue edema formation. These results indicate that beta-agonists suppress vascular permeability response and local tissue edema formation not by inhibiting mast cell degranulation, but by inhibiting the reactivity of the local vasculature to chemical mediators such as arachidonate metabolites, PAF, and histamine and serotonin released from mast cells.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Role of phosphatidylinositol 3-kinase in degranulation induced by IgE-dependent and -independent mechanisms in rat basophilic RBL-2H3 (ml) cells.

We have examined the role of phosphatidylinositol 3-kinase (P13-kinase) in the degranulation induced by the antigen, an IgE-dependent stimulant, and by carbachol and thapsigargin, IgE-independent stimulants, in the muscarine ml receptor-transfected mast cell line RBL-2h3 (ml) cells. These stimulants commonly increased P13-kinase activity in the anti-phosphotyrosine immunoprecipitate. The P13-kinase inhibitors wortmannin and LY294002 inhibited induced by these stimulants. The membrane ruffling induced by the antigen or carbachol was also inhibited by wortmannin. In contrast, thapsigargin induced by membrane ruffling but induced microspikes, which was not affected by wortmannin. In the permeabilized RBL-2H3 (ml) cells, wortmannin the GTP gamma S-induced membrane ruffling without inhibiting the GTP gamma S-induced degranulation. These findings suggest that P13-kinase is involved not only in IgE-dependent degranulation but also in IgE-independent degranulation, and that the GTP gamma S-sensitive protein at the downstream of P13-kinase is responsible for the degranulation but not for the membrane ruffling.

Androstadienes↗
PubMedDate not supplied

Negative regulation of MAP kinase by diacylglycerol-dependent mechanisms via G protein-coupled receptors in rat basophilic RBL-2H3 (ml) cells.

Carbachol and 5'-(N-ethylcarboxamido)-adenosine (NECA), stimulants of G protein-coupled receptors, induce MAP kinase activation in the muscarinic ml receptor-transfected mast cell line, RBL-2H3 (ml) cells. The phospholipase C inhibitor neomycin and the phosphatidate phosphohydrolase inhibitor propranolol augmented MAP kinase activation induced by carbachol and NECA without affecting the antigen-induced MAP kinase activation. Furthermore, the duration of MAP kinase activation induced by carbachol or NECA was also prolonged by neomycin and propranolol. The specific protein kinase C inhibitor Ro 31-8425 enhanced the carbachol- or NECA-induced MAP kinase activation. These findings suggest that the MAP kinase activation mediated by the G protein-coupled receptors is negatively regulated by diacylglycerol and activated protein kinase C(s).

Adenosine↗