A study of the synergism between metabotropic glutamate receptor activation and arachidonic acid in the rat hippocampus.
We report that activation of the metabotropic glutamate receptor by the specific agonist, trans-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD), increases release of glutamate only in the presence of a low concentration of arachidonic acid (AA). To identify the molecular mechanism underlying this effect, cAMP accumulation, inositol phospholipid metabolism and protein kinase C (PKC) activation were examined in synaptosomes prepared from hippocampus. ACPD increased cAMP accumulation, but this increase was not further enhanced in the presence of AA. ACPD and AA stimulated both inositol phospholipid turnover and PKC activity; a synergistic action was indicated by the additional stimulation in the presence of both agents. The increase in PKC activity, either directly, or indirectly by increased inositol phospholipid turnover, might therefore underlie the enhanced glutamate release.
McGahon
B
B
Department of Physiology, Trinity College, Dublin, Ireland.
Lynch
M A
MA
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism
D010716:Phosphatidylinositols; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D016718:Arachidonic Acid; D018698:Glutamic Acid; D000242:Cyclic AMP; D011493:Protein Kinase C