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Protein Kinase C‐Mediated Suppression of the Presynaptic Adenosine A1 Receptor by a Facilitatory Metabotropic Glutamate Receptor
Author(s) -
Budd David C.,
Nicholls David G.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65020615.x
Subject(s) - protein kinase c , adenosine , glutamate receptor , metabotropic glutamate receptor , acpd , agonist , metabotropic receptor , biology , metabotropic glutamate receptor 5 , medicine , adenosine a1 receptor , adenosine receptor antagonist , adenosine receptor , endocrinology , chemistry , pharmacology , receptor , biochemistry , phosphorylation
KCl‐evoked glutamate exocytosis from cerebrocortical synaptosomes can be inhibited by the adenosine A1 receptor agonist cyclohexyladenosine (CHA). Inhibition is associated with a decreased KCl‐evoked Ca 2+ level elevation, and the effect of the agonist is occluded by prior incubation with the Agelenopsis aperta neurotoxin ω‐agatoxin‐IVA at 250 n M . The inhibition is suppressed in the presence of 3 n M phorbol dibutyrate (PDBu) or by activation of the protein kinase C (PKC)‐coupled metabotropic glutamate receptor by 100 µ M (1 S ,3 R )‐1‐aminocyclopentane‐1,3‐dicarboxylate [(1 S ,3 R )ACPD]. A tonic inhibition of release by leaked exogenous adenosine can be reversed by adenosine deaminase or by PDBu addition. The CHA‐induced inhibition can be enhanced by the PKC inhibitor Ro 31‐8220. The mechanism for the suppression of the adenosine A1 receptor‐mediated inhibition is distinct from that previously described for the (1 S ,3 R )ACPD‐evoked, PKC‐mediated, facilitatory pathway, which enhances phosphorylation of the MARCKS protein, 4‐aminopyridine‐induced action potentials, and release of glutamate because the latter requires at least 100 n M PDBu [or the combination of (1 S ,3 R )ACPD and arachidonic acid] and is not seen following KCl depolarization. Both PKC‐mediated pathways may be involved in the presynaptic events associated with the establishment of synaptic plasticity.