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Presynaptic GABA B Receptor Modulation of Glutamate Exocytosis from Rat Cerebrocortical Nerve Terminals: Receptor Decoupling by Protein Kinase C
Author(s) -
Perkinton Michael S.,
Sihra Talvinder S.
Publication year - 1998
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.1471-4159.1998.70041513.x
Subject(s) - glutamate receptor , baclofen , gabab receptor , agonist , chemistry , protein kinase c , synaptosome , 4 aminopyridine , pharmacology , receptor , biophysics , biology , biochemistry , signal transduction , potassium channel , membrane
Abstract: GABA and the GABA B receptor agonist (−)‐baclofen inhibited 4‐aminopyridine (4AP)‐ and KCl‐evoked, Ca 2+ ‐dependent glutamate release from rat cerebrocortical synaptosomes. The GABA B receptor antagonist CGP 35348, prevented this inhibition of glutamate release, but phaclofen had no effect. (−)‐Baclofen‐mediated inhibition of glutamate release was insensitive to 2 µg/ml pertussis toxin. As determined by examining the mechanism of GABA B receptor modulation of glutamate release, (−)‐baclofen caused a significant reduction in 4AP‐evoked Ca 2+ influx into synaptosomes. The agonist did not alter the resting synaptosomal membrane potential or 4AP‐mediated depolarization; thus, the inhibition of Ca 2+ influx could not be attributed to GABA B receptor activation causing a decrease in synaptosomal excitability. Ionomycin‐mediated glutamate release was not affected by (−)‐baclofen, indicating that GABA B receptors in this preparation are not coupled directly to the exocytotic machinery. Instead, the data invoke a direct coupling of GABA B receptors to voltage‐dependent Ca 2+ channels linked to glutamate release. This coupling was subject to regulation by protein kinase C (PKC), because (−)‐baclofen‐mediated inhibition of 4AP‐evoked glutamate release was reversed when PKC was stimulated with phorbol ester. This may therefore represent a mechanism by which inhibitory and facilitatory presynaptic receptor inputs interplay to fine‐tune transmitter release.