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Presynaptic k‐Opioid and Muscarinic Receptors Inhibit the Calcium‐Dependent Component of Evoked Glutamate Release from Striatal Synaptosomes
Author(s) -
Rawls Scott M,
McGinty Jacqueline F,
Terrian David M
Publication year - 1999
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.1471-4159.1999.0731058.x
Subject(s) - glutamate receptor , chemistry , metabotropic glutamate receptor , agonist , muscarinic acetylcholine receptor , pharmacology , endocrinology , medicine , receptor , biology , biochemistry
: In addition to cytosolic efflux, reversal of excitatory amino acid (EAA) transporters evokes glutamate exocytosis from the striatum in vivo. Both k‐opioid and muscarinic receptor agonists suppress this calcium‐dependent response. These data led to the hypothesis that the calcium‐independent efflux of striatal glutamate evoked by transporter reversal may activate a transsynaptic feedback loop that promotes glutamate exocytosis from thalamo‐ and/or corticostriatal terminals in vivo and that this activation is inhibited by presynaptic k and muscarinic receptors. Corollaries to this hypothesis are the predictions that agonists for these putative presynaptic receptors will selectively inhibit the calcium‐dependent component of glutamate released from striatal synaptosomes, whereas the calcium‐independent efflux evoked by an EAA transporter blocker, L‐ trans ‐pyrrolidine‐2,4‐dicarboxylic acid (L‐ trans ‐PDC), will be insensitive to such receptor ligands. Here we report that a muscarinic agonist, oxotremorine (0.01‐10 μ M ), and a k‐opioid agonist, U‐69593 (0.1‐100 μ M ), suppressed the calcium‐dependent release of glutamate that was evoked by exposing striatal synaptosomes to the potassium channel blocker 4‐aminopyridine. The presynaptic inhibition produced by these ligands was concentration dependent, blocked by appropriate receptor antagonists, and not mimicked by the δ‐opioid agonist [D‐Pen 2,5 ]‐enkephalin. The finding that glutamate efflux evoked by L‐ trans ‐PDC from isolated striatal nerve endings was entirely calcium independent supports the notion that intact basal ganglia circuitry mediates the calcium‐dependent effects of this agent on glutamate efflux in vivo. Furthermore, because muscarinic or k‐opioid receptor activation inhibits calcium‐dependent striatal glutamate release in vitro as it does in vivo, it is likely that both muscarinic and k receptors are inhibitory presynaptic heteroceptors expressed by striatal glutamatergic terminals.