Activation of phospholipase D by metabotropic glutamate receptor agonists in rat cerebrocortical synaptosomes

Shinomura, T., del Río, E., Breen, K.C., Downes, C.P. and McLaughlin, M. (2000) Activation of phospholipase D by metabotropic glutamate receptor agonists in rat cerebrocortical synaptosomes. British Journal of Pharmacology, 131(5), pp. 1011-1018. (doi:10.1038/sj.bjp.0703651) (PMID:11053224) (PMCID:PMC1572410)

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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 [3H]‐arachidonic acid or [32P]‐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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McLaughlin, Dr Mark
Authors: Shinomura, T., del Río, E., Breen, K.C., Downes, C.P., and McLaughlin, M.
College/School:College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:British Journal of Pharmacology
Publisher:Wiley
ISSN:0007-1188
ISSN (Online):1476-5381

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