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GABA and glutamate release affected by GABA B receptor antagonists with similar potency: no evidence for pharmacologically different presynaptic receptors
Author(s) -
Waldmeier Peter C.,
Wicki Peter,
Feldtrauer JeanJacques,
Mickel Stuart J.,
Bittiger Helmut,
Baumann Peter A.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17168.x
Subject(s) - baclofen , gabab receptor , autoreceptor , agonist , glutamate receptor , chemistry , pharmacology , stimulation , receptor , biology , neuroscience , biochemistry
1 The effects of a series of nine GABA B receptor antagonists of widely varying potencies on electrically stimulated release from cortical slices of [ 3 H]‐GABA in the absence or presence of 10 μ m of the GABA B agonist, (−)−baclofen and of endogenous glutamate in the presence of (−)−baclofen were compared. 2 The concentrations of the compounds half maximally increasing [ 3 H]‐GABA release (EC 50 's) at a stimulation frequency of 2 Hz correlated well with the IC 50 values obtained from the inhibition of the binding of the agonist, [ 3 H]‐CGP 27492, to GABA B receptors in rat brain membranes (rank order of potency: CGP 56999 A ≥ CGP 55845 A > CGP 52432 ≥ CGP 56433 A > CGP 57034 A > CGP 57070 A ≥ CGP 57976 > CGP 51176 > CGP 35348). 3 Likewise, the concentrations causing half‐maximal increases of [ 3 H]‐GABA in the absence or presence of (−)−baclofen, and of endogenous glutamate in the presence of (−)−baclofen, correlated well with each other. Reports in the literature suggesting the CGP 35348 exhibits a 70 fold preference for inhibition of (−)−baclofen's effects on glutamate over [ 3 H]‐GABA release, and that CGP 52432 shows a 100 fold preference in the opposite sense, could not be confirmed in our model. 4 Therefore, our results suggest that, if there are pharmacological differences between GABA B autoreceptors and GABA B heteroreceptors on glutamatergic nerve endings in the rat cortex, they are not revealed by this series of compounds of widely different potencies. 5 In particular, our results with CGP 35348 and CGP 52432 do not support the hypothesis that GABA B autoreceptors and GABA B heteroreceptors on glutamatergic nerve endings represent subtypes with different pharmacology.