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Adenosine A 1 Receptor Inhibition of Glutamate Exocytosis and Protein Kinase C‐Mediated Decoupling
Author(s) -
Banie Anne P.,
Nicholls David G.
Publication year - 1993
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 - 10.1111/j.1471-4159.1993.tb03257.x
Subject(s) - exocytosis , adenosine a2b receptor , glutamate receptor , chemistry , adenosine , protein kinase c , microbiology and biotechnology , adenosine receptor , receptor , pharmacology , biochemistry , biology , kinase , agonist , membrane
The adenosine modulation of glutamate exoeytosis from guinea pig cerebrocortical synaptosomes is investigated. Endogenously leaked adenosine is sufficient to cause a partial tonic inhibition of 4‐aminopyridine‐evoked glutamate release, which can be relieved by adenosine deaminase. The adenosine A 1 receptor is equally effective in mediating inhibition of glutamate exocytosis evoked by 4‐aminopyridine (where K + ‐channel activation would inhibit release) and by elevated KC1 (where K + ‐channel activation would have no effect), arguing for a central role of Ca 2+ ‐channel modulation. In support of this, the plateau phase of depolarization‐evoked free Ca 2+ elevation is decreased by adenosine with both depolarization protocols. No effect of adenosine agonists is seen on membrane potential in polarized or KC1‐ or 4‐aminopyridine‐stimulated synaptosomes. The interaction of protein kinase C with the A 1 receptormediated inhibition is examined. Activation of protein kinase C by 4β‐phorbol dibutyrate has been shown previously by this laboratory to modulate glutamate release via K + ‐channel inhibition, and is shown here to have an additional action of decoupling the adenosine inhibition of glutamate exocytosis.