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Molecular and pharmacological evidence for a facilitatory functional role of pre‐synaptic GLUK 2/3 kainate receptors on GABA release in rat trigeminal caudal nucleus
Author(s) -
Samengo I.,
Currò D.,
Navarra P.,
Barrese V.,
Taglialatela M.,
Martire M.
Publication year - 2012
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/j.1532-2149.2012.00122.x
Subject(s) - kainate receptor , ampa receptor , chemistry , gabaa receptor , ionotropic effect , glutamate receptor , neurotransmission , receptor , nbqx , long term potentiation , agonist , biophysics , biochemistry , biology
Background Gamma‐aminobutyric acid ( GABA ) and glutamate ( GLU ) are involved in nociceptive signals processing in the trigeminal system. In this study, we investigated the influence of excitatory transmission on GABA release in nerve terminals isolated from the rat trigeminal caudal nucleus ( TCN ). Methods We utilize biochemical (superfused synaptosomes loaded with [ 3 H ] GABA ) and morphological (immunofluorescence experiments with specific antibody) techniques. Results Our results show that GLU potentiates the release of [ 3 H ] GABA evoked by 9, 15 and 30 m M [K + ] e ; 15 m M [K + ] e ‐evoked [ 3 H ] GABA release was also reinforced by domoate and kainate ( KA ), two naturally occurring GLU ‐receptor agonists. The enhancement of 15 m M [K + ] e ‐evoked [ 3 H ] GABA release produced by 100 μ M KA was abolished by NBQX , a mixed AMPA / KA receptor antagonist, but was not affected by GYK I52466, a selective AMPA receptor antagonist. ATPA , a selective agonist for KA receptors containing the GLUK 1 subunit, had no effect on depolarization‐induced [ 3 H ] GABA release, and UBP 310, which selectively antagonizes these same receptors, failed to reverse the KA ‐induced potentiation of 15 m M [K + ] e ‐evoked [ 3 H ] GABA release. The KA ‐induced potentiation was also unaffected by concanavalin A (10 μ M ), a positive allosteric modulator of GLUK 1‐ and GLUK 2‐containing KA receptors. Immunofluorescence experiments revealed that GABA ergic nerve terminals in the TCN differentially expressed GLUK subunits, with GLUK 2/3‐positive terminals being twice more abundant than GLUK 1‐containing synaptosomes. Conclusions These findings indicate that pre‐synaptic KA receptors facilitating GABA release from TCN nerve terminals mainly express GLUK2/GLUK3 subunits, supporting the notion that different types of KA receptors are involved in the various stages of pain transmission.