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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Shinomura, T. Breen, K. C. Downes, C. P. Del Río, E. Mclaughlin, M. |
| Description | Author Affiliation: Shinomura T ( Department of Pharmacology and Neuroscience, Ninewells Hospital Medical School, University of Dundee, Dundee, DD1 9SY. shino@kuhp.kyoto-u.ac.jp) |
| Abstract | The pharmacological profile of metabotropic glutamate receptor (mGluR) activation of phospholipase D (PLD), and the associated signalling pathways, were examined in rat cerebrocortical synaptosomes. The assay was conducted using a transphosphatidylation reaction in synaptosomes which were pre-labelled with either [(3)H]-arachidonic acid or [(32)P]-orthophosphate. The mGluR agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S, 3R-ACPD) and (RS)-3,5-dihydroxyphenylglycine (DHPG), both activated PLD, while phorbol 12,13-dibutyrate (PDBu) treatment caused receptor-independent activation of PLD and had an additive effect on 1S,3R-ACPD induced PLD activity. A protein kinase C (PKC) inhibitor, GF109203X, failed to antagonize mGluR receptor-coupled PLD activity. We could not detect any increase in the products of PI (phosphoinositide)-specific phospholipase C (PI-PLC), inositol(1,4, 5)trisphosphate or diacylglycerol, by 1S, 3R-ACPD at 15 s. However, diacylglycerol increased monophasically in response to mGluR agonists and remained elevated for at least 15 min. Phosphatidic acid phosphohydrolase (PAP) activity, which converts PA to DAG, was present in the synaptosomes. These data suggest that, in rat cerebrocortical synaptosomes, the 1S,3R-ACPD-sensitive mGluR is coupled to PLD through a mechanism that is independent of both PKC and PI-PLC. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 131 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2000-11-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Cerebral Cortex Enzymology Excitatory Amino Acid Agonists Pharmacology Phospholipase D Metabolism Receptors, Metabotropic Glutamate Agonists Synaptosomes Animals Diglycerides Biosynthesis Enzyme Activation Drug Effects Methoxyhydroxyphenylglycol Analogs & Derivatives Phorbol 12,13-Dibutyrate Phosphatidylinositol Diacylglycerol-Lyase Phosphoinositide Phospholipase C Protein Kinase C Physiology Rats, Wistar Type C Phospholipases Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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