2-(4-amylcinnamoyl)amino-4-chlorobenzoic-acid and 1-6-bis(cyclohexyloximinocarbonyl)hexane

Pulmonary infection by

Topics: Animals; Arachidonic Acid; Bacteremia; Cell Line, Tumor; Chemotactic Factors; Chlorobenzoates; Cinnamates; Cyclohexanones; Enzyme Inhibitors; Epithelial Cells; Group IV Phospholipases A2; Host-Pathogen Interactions; Humans; Lung; Mice; Mice, Inbred BALB C; Mice, Knockout; Neutrophil Infiltration; Neutrophils; ortho-Aminobenzoates; Pneumococcal Infections; Pneumonia, Bacterial; Streptococcus pneumoniae; Survival Analysis; Transendothelial and Transepithelial Migration

The protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu) induced the release of both luteinizing hormone (LH) and growth hormone (GH) from proestrous rat anterior pituitary pieces in vitro. Phorbol 12,13-dibutyrate-induced LH, but not GH release was readily inhibited by the phospholipase A2 (PLA2) inhibitors, quinacrine, aristolochic acid, ONO-RS-082 and chloracysine. Furthermore, PDBu induced release of [3H]arachidonic acid ([3H]AA) from pre-labelled anterior pituitary tissue that was prevented in the presence of quinacrine, aristolochic acid and ONO-RS-082 but not the diglyceride lipase inhibitor RHC 80267. The effect of PDBu was completely inhibited by staurosporine and the selective PKC inhibitor Ro 31-8220 but only partially by low concentrations of H7; consistent with the involvement of both H7-sensitive and H7-resistant forms of PKC in the activation of PLA2 by PDBu. The protein synthesis inhibitor cycloheximide inhibited the release of both [3H]AA and LH that had been induced by PDBu, whereas LH release induced by the PLA2 activator mellitin was cycloheximide-insensitive. These results suggest that PKC activators may induce LH but not GH release from anterior pituitary tissue by a mechanism involving activation of a PLA2, brought about by a process which is reliant on protein synthesis.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Alkaloids; Aminobenzoates; Animals; Arachidonic Acid; Aristolochic Acids; Chlorobenzoates; Cinnamates; Cyclohexanones; Cycloheximide; Enzyme Activation; Female; Growth Hormone; Indoles; Ionomycin; Isoquinolines; Luteinizing Hormone; Melitten; ortho-Aminobenzoates; Phenanthrenes; Phenothiazines; Phorbol 12,13-Dibutyrate; Phospholipases A; Phospholipases A2; Piperazines; Pituitary Gland, Anterior; Proestrus; Protein Kinase C; Quinacrine; Rats; Rats, Wistar; Signal Transduction; Staurosporine

Phospholipase A2 enzymatic activity was measured in the teratoma-derived adipogenic cell line 1246 and in adipocyte precursors in primary cultures. It was shown that enzymatic activity was low while the cells were undifferentiated and increased by 20-24-fold after the cells had undergone adipocyte differentiation. The increase of phospholipase A2 activity follows the same time course as that observed for glycerol-3-phosphate dehydrogenase activity used as a marker of differentiation. In contrast, the differentiation-deficient, insulin-independent cell line 1246-3A always contained very low levels of phospholipase A2 activity. Phospholipase A2 activity measured in the 1246 cells was inhibited in a dose-dependent fashion by incubation with ONO-RS-082 and quinacrine which are inhibitors of phospholipase A2 activity. Measurements of arachidonate metabolites in 1246 cells showed that production of prostaglandin F2 alpha by the 1246 cells followed the same time course as the increase of phospholipase A2 activity during differentiation. Similar results were obtained with primary cultures of adipocyte precursors. These results indicate that phospholipase A2 is a differentiation-dependent enzymatic activity for the adipogenic cell line 1246 and for adipocyte precursors in primary culture. These data suggest that metabolic pathways controlled by phospholipase A2 activity could play an important physiological role in adipose tissue differentiation.

Topics: Adipose Tissue; Aminobenzoates; Animals; Arachidonic Acids; Cell Differentiation; Cell Line; Chlorobenzoates; Cinnamates; Cyclohexanones; Glyceraldehyde-3-Phosphate Dehydrogenases; Kinetics; ortho-Aminobenzoates; Phospholipases; Phospholipases A; Phospholipases A2; Prostaglandins; Quinacrine; Radioimmunoassay; Teratoma; Thromboxane B2