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Activation of phospholipase D by metabotropic glutamate receptor agonists in rat cerebrocortical synaptosomes
Author(s) -
Shinomura T,
Del Río E,
Breen K C,
Downes C P,
McLaughlin M
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703651
Subject(s) - metabotropic glutamate receptor , metabotropic glutamate receptor 5 , acpd , phospholipase d , protein kinase c , phospholipase c , diacylglycerol kinase , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 7 , chemistry , synaptosome , metabotropic receptor , agonist , biochemistry , biology , receptor , signal transduction , membrane
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.British Journal of Pharmacology (2000) 131 , 1011–1018; doi: 10.1038/sj.bjp.0703651