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Biomedical subjects

F Hirata

Publications and source records attributed to F Hirata.

At least 145 records · Page 8Linked to original sources
PubMed1980

Phospholipid methylation and the transmission of biological signals through membranes.

Enzymatic methylation of phosphotidylethanolamine (PE) to form phosphatidylcholine (PC) is associated with translocation of the lipid from the inner cell membrane (PE) to the outer membrane (PC), a concomitant decrease in membrane viscosity, and in some cases, activation of phospholipase A and release of arachidonic acid. Changes in phospholipid methylation are induced by a variety of ligands upon interaction with their specific receptors. In each case stimulation of phospholipid methylation appears to contribute to the propagation of the particular physiological response (e.g., activation of adenylate cyclase in rat reticulocytes; release of histamine by mast cells; chemotactic movement of neutrophils; mitogenesis of lymphocytes). Thus, receptor-mediated changes in phospholipid methylation and membrane fluidity may represent a general mechanism leading to a specific cellular response.

Animals↗
PubMed1980

Phospholipid methylation: a biochemical signal modulating lymphocyte mitogenesis.

Phospholipid methylation in murine T lymphocytes but not B cells was stimulated by mitogenic lectins such as concanavalin A and phytohemagglutinin, and the methylation was then returned to the control level by the concomitant activation of phospholipase A2. A parallelism between dose-response curves of concanavalin A for phospholipid methylation and thymidine incorporation was found. Inhibition of either synthesis or degradation of methylated phospholipids resulted in a decrease in the thymidine incorporation. Although prostaglandins such as the E and F series were the main products of arachidonic acid released by phospholipase A2 activation, inhibition of synthesis of these compounds by indomethacin did not reduce the thymidine incorporation significantly. These results suggest that the mitogenesis of murine T lymphocytes is triggered by the activation of both phospholipid methyltransferase(s) and phospholipase A2.

Animals↗
PubMed1980

Mepacrine blocks beta-adrenergic agonist-induced desensitization in astrocytoma cells.

C6 astrocytoma cells contain beta-adrenergic receptors coupled to adenylate cyclase. A 2-hr exposure to l-isoproterenol results in an 80% decrease in cyclic AMP production in response to a subsequent challenge by l-isoproterenol (desensitization). This loss in responsiveness is paralleled by a 20-30% decrease in the apparent number of beta-adrenergic receptors and by increased release of arachidonic aciid into the medium. The increased release of arachidonic acid is caused by the action of phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) and corresponds to increased turnover of methylated phospholipids. Mepacrine and tetracaine, both inhibitors of this phospholipase A2, are able to block l-isoproterenol-induced desensitization of cyclic AMP production and the decrease in beta-adrenergic receptors. Mellitin and phorbol ester, two activators of phospholipase A2, when preincubated with the cells cause a decreased cyclic AMP response of the cells to l-isoproterenol. These results suggest that the activation of phospholipase A2 in the local domain of the beta-adrenergic receptor may be involved in desensitization.

Adenylyl Cyclases↗
PubMed1980

Stimulation of phospholipid methylation, Ca2+ influx, and histamine release by bridging of IgE receptors on rat mast cells.

Normal rat mast cells were stimulated by antibodies against IgE receptors (anti-RBL) or by anti-IgE, and [3H]methyl group incorporation into phospholipids, 45Ca uptake, and histamine release were examined. Anti-RBL or its F(ab')2 fragments and anti-IgE induced an increase in the incorporation of [3H]methyl into phospholipids, in 45Ca influx, and in histamine release. By contrast, Fab' monomer fragments of anti-RBL induced none of these reactions. The transient increase of [3H]methyl incorporation in lipids peaked within 15 sec after the addition of either anti-RBL or anti-IgE and fell to basal level in 30 sec. This was then followed by an influx of 45Ca that increased to a maximum in 2 min and by histamine release that reached a maximum in 3 min. Inhibition of phospholipid methylation resulted in an inhibition of 45Ca influx and histamine release. These findings demonstrate that phospholipid methylation in rat mast cells is induced by bridging of IgE receptors on the cell surface and that increased methylation of phospholipids sets the stage for an influx of Ca2+ and subsequent release of histamine.

Animals↗
PubMed1980

A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids.

When rabbit peritoneal neutrophils were treated with glucocorticoids, their chemotactic response to stimulation by the chemoattractant fMet-Leu-Phe was markedly reduced. Preincubation of cells with glucocorticoids also decreased phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) activity in situ as measured by the release of [1-14C]arachidonic acid previously incorporated into phospholipids. The inhibitory potencies of glucocorticoids on phospholipase A2 activity correlated well with their anti-inflammatory activities and their abilities to bind to glucocorticoid receptors. Inhibitors of RNA and protein synthesis suppressed the inhibitory effect of glucocorticoids on phospholipase A2 activity. Digestion of the glucocorticoid-treated cells by Pronase overcame the inhibitory activity. Phospholipase A2 activity induced by Ca2+ ionophore A23187 was not affected by Pronase treatment. Gel filtration of proteins from neutrophil membranes labeled with [3H]lysine showed an induction of protein(s) (about 40,000 daltons) after glucocorticoid treatment. This protein inhibited a partially purified pancreatic phospholipase A2 and reduced the peptide-initiated chemotactic response of neutrophils.

Animals↗
PubMed1980

Studies on antitumor polysaccharides, especially D-II, from mycelium of Coriolus versicolor.

A water-soluble polysaccharide, D-II with marked antitumor activity was isolated from the cultured mycelium of Coriolus versicolor by extraction with hot-water, fractional precipitation with ethanol and ion-exchange chromatography. D-II strongly inhibited the growth of Sarcoma-180 transplanted subcutaneously in mice by intraperitoneal, intravenous, subcutaneous or intra-muscular administration at a dose of 5 mg/kg. the molecular weight was estimated to be 2,000,000 by gel-filtration or 6,500,000 by light scattering analysis. The chemical structure of D-II was then investigated by periodate oxidation, methylation analysis, Smith degradation, and a combination of controlled Smith degradation and methylation analysis. These studies proposed that D-II is composed of a unit structure of four D-glucose residues, and is a glucan consisting of beta-D-1,3-linked main chain in which one for every three D-glucose residues is branched at C-6 with beta-D-1,6-linkage.

Animals↗
PubMed1979

Phospholipid methylation unmasks cryptic beta-adrenergic receptors in rat reticulocytes.

The effect of phospholipid methylation on the number of beta-adrenergic receptor binding sites was examined in rat reticulocyte membranes. Stimulation of phosphatidylcholine synthesis by the introduction of the methyl donor S-adenosyl-L-methionine into reticulocyte ghosts increased the number of beta-adrenergic receptor sites. The appearance of beta-adrenergic binding sites was dependent on the formation of phosphatidylcholine by the enzyme that converts phosphatidyl-N-monomethylethanolamine from phosphatidylethanolamine. Both the synthesis of phosphatidylcholine and the unmasking of cryptic receptors were time and temperature dependent and did not occur in the presence of the methyl transferase inhibitor, S-adenosyl-L-homocysteine.

Animals↗