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Characterisation of the effects of ATPA, a GLU(K5) kainate receptor agonist, on GABAergic synaptic transmission in the CA1 region of rat hippocampal slices.
Neuropharmacology. 2004 Sep; 47(3):363-72.N

Abstract

Kainate receptors are implicated in a variety of physiological and pathological processes in the CNS. Previously we demonstrated that (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA), a selective agonist for the GLU(K5) subtype of kainate receptor, depresses monosynaptically evoked inhibitory postsynaptic potentials (IPSPs) in the CA1 region of the rat hippocampus. In the current study, we provide a more detailed characterisation of this effect. Firstly, our data demonstrate a rank order of potency of domoate>kainate>ATPA>alpha-amino-3-(3-hydroxy-5-methyl-4-isoxalolyl)propionic acid Secondly, we confirm that the effects of ATPA are not mediated indirectly via the activation of gamma-aminobutyric acid receptors (i.e. either GABA(A) or GABA(B)). Thirdly, we show that the small increase in conductance induced by ATPA is insufficient to account for the depression of monosynaptic inhibition. Fourthly, we show that the effects of ATPA on IPSPs are antagonised by the GLU(K5)-selective antagonist (3S, 4aR, 6S, 8aR)-6-(4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid (LY382884). However, LY382884 is less potent as an antagonist of the effects of ATPA on IPSPs compared to its depressant effect on EPSPs.

Authors+Show Affiliations

MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, University Walk, Bristol BS8 1TD, UK. v.r.clarke@bris.ac.ukNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15275825

Citation

Clarke, V R J., and G L. Collingridge. "Characterisation of the Effects of ATPA, a GLU(K5) Kainate Receptor Agonist, On GABAergic Synaptic Transmission in the CA1 Region of Rat Hippocampal Slices." Neuropharmacology, vol. 47, no. 3, 2004, pp. 363-72.
Clarke VR, Collingridge GL. Characterisation of the effects of ATPA, a GLU(K5) kainate receptor agonist, on GABAergic synaptic transmission in the CA1 region of rat hippocampal slices. Neuropharmacology. 2004;47(3):363-72.
Clarke, V. R., & Collingridge, G. L. (2004). Characterisation of the effects of ATPA, a GLU(K5) kainate receptor agonist, on GABAergic synaptic transmission in the CA1 region of rat hippocampal slices. Neuropharmacology, 47(3), 363-72.
Clarke VR, Collingridge GL. Characterisation of the Effects of ATPA, a GLU(K5) Kainate Receptor Agonist, On GABAergic Synaptic Transmission in the CA1 Region of Rat Hippocampal Slices. Neuropharmacology. 2004;47(3):363-72. PubMed PMID: 15275825.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterisation of the effects of ATPA, a GLU(K5) kainate receptor agonist, on GABAergic synaptic transmission in the CA1 region of rat hippocampal slices. AU - Clarke,V R J, AU - Collingridge,G L, PY - 2004/02/16/received PY - 2004/05/03/revised PY - 2004/05/07/accepted PY - 2004/7/28/pubmed PY - 2004/12/16/medline PY - 2004/7/28/entrez SP - 363 EP - 72 JF - Neuropharmacology JO - Neuropharmacology VL - 47 IS - 3 N2 - Kainate receptors are implicated in a variety of physiological and pathological processes in the CNS. Previously we demonstrated that (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA), a selective agonist for the GLU(K5) subtype of kainate receptor, depresses monosynaptically evoked inhibitory postsynaptic potentials (IPSPs) in the CA1 region of the rat hippocampus. In the current study, we provide a more detailed characterisation of this effect. Firstly, our data demonstrate a rank order of potency of domoate>kainate>ATPA>alpha-amino-3-(3-hydroxy-5-methyl-4-isoxalolyl)propionic acid Secondly, we confirm that the effects of ATPA are not mediated indirectly via the activation of gamma-aminobutyric acid receptors (i.e. either GABA(A) or GABA(B)). Thirdly, we show that the small increase in conductance induced by ATPA is insufficient to account for the depression of monosynaptic inhibition. Fourthly, we show that the effects of ATPA on IPSPs are antagonised by the GLU(K5)-selective antagonist (3S, 4aR, 6S, 8aR)-6-(4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid (LY382884). However, LY382884 is less potent as an antagonist of the effects of ATPA on IPSPs compared to its depressant effect on EPSPs. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/15275825/Characterisation_of_the_effects_of_ATPA_a_GLU_K5__kainate_receptor_agonist_on_GABAergic_synaptic_transmission_in_the_CA1_region_of_rat_hippocampal_slices_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028390804001376 DB - PRIME DP - Unbound Medicine ER -