sq-23377 and 2-(4-amylcinnamoyl)amino-4-chlorobenzoic-acid

1. Uridine triphosphate (UTP), uridine diphosphate (UDP), cytidine triphosphate (CTP), and deoxythymidine triphosphate (TTP) caused concentration-dependent increases in the release of thromboxane A2 (TXA2) from cultured glia prepared from the newborn rat cerebral cortex. Although each of the pyrimidine nucleotides displayed similar potencies, CTP and TTP were considerably less effective than either UTP or UDP. The purine nucleotide ATP was equally as potent as the pyrimidine nucleotides but was marginally less effective than either UTP or UDP. 2. The ability of UTP, UDP, TTP, and CTP to promote TXA2 release from cultured glia was inhibited in a concentration-dependent manner by suramin and was markedly reduced when incubations were performed either in Ca(2+)-free medium or on cultures which had been maintained in serum-free growth medium for 4 days prior to experimentation. 3. Challenges with UTP and UDP in combination were found to elicit a response which was no different from the effects of these nucleotides alone; in addition, their effects were reversed by the phospholipase A2 inhibitor ONO-RS-082. A slight reduction in UTP- and UDP-stimulated TXA2 release was observed in cultures grown in the presence of leucine methyl ester, a treatment reported to limit microglial survival. 4. These results suggest that glia are targets for extracellular pyrimidine nucleotides and that their ability to release eicosanoids from these cells may be important in the brain's response to damage.

Topics: Aminobenzoates; Animals; Animals, Newborn; Calcium; Cells, Cultured; Cerebral Cortex; Chlorobenzoates; Cinnamates; Culture Media, Serum-Free; Cytidine Triphosphate; Drug Interactions; Ionomycin; Ionophores; Leucine; Neuroglia; ortho-Aminobenzoates; Phospholipases A; Phospholipases A2; Rats; Thromboxane A2; Thymine Nucleotides; Uridine Diphosphate; Uridine Triphosphate

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