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 KCI-evoked exocytotic release of glutamate from rat cerebrocortical synaptosomes is inhibited by a presynaptic adenosine Al 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 mu M 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. (C) 1998 Elsevier Science Ireland Ltd.