Arachidonic acid potentiates the duration of the metabotropic, protein kinase C-mediated, suppression of the inhibitory adenosine A1 receptor pathway in glutamatergic nerve terminals from rat cerebral cortex.
The KCl-evoked exocytotic release of glutamate from rat cerebrocortical synaptosomes is inhibited by a presynaptic adenosine A1 receptor decreasing voltage-activated Ca2+ entry. This inhibition was transiently suppressed by (1S,3R)-1-aminocyclopenthyl-1,3-dicarboxylate (ACPD) but was restored within 1 min in the continued presence of the metabotropic agonist. In the presence of 2 microM arachidonic acid ACPD initiated a prolonged suppression of the adenosine-mediated inhibition persisting for at least 10 min. Arachidonic acid (20-40 pmol) was bound per mg synaptosomal protein. Prolonged ACPD-mediated phosphorylation of the protein kinase C (PKC) substrate myristoylated alanine-rich C-kinase substrate (MARCKS) was detected in the presence but not the absence of arachidonic acid, but arachidonic acid added 2 min after ACPD was ineffective. It is concluded that arachidonic acid synergistically prolongs the metabotropic glutamate receptor-mediated activation of presynaptic PKC, suppressing inhibitory receptor pathways.
Budd
D C
DC
The Neurosciences Institute, Department of Pharmacology, Ninewells Medical School, University of Dundee, UK.
Nicholls
D G
DG
D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology*; D002540:Cerebral Cortex / Q000201:enzymology / Q000502:physiology*; D017729:Presynaptic Terminals / Q000201:enzymology / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013574:Synaptosomes / Q000201:enzymology / Q000502:physiology
D018094:Receptors, Metabotropic Glutamate; D018047:Receptors, Purinergic P1; D016718:Arachidonic Acid; D011493:Protein Kinase C