Inhibition of [ 3H]γ-aminobutyric acid release by kainate receptor activation in rat hippocampal synaptosomes

We studied the modulation of γ-aminobutyric acid (GABA) release by activation of kainate receptor in rat whole hippocampal synaptosomes. Kainate (10–300 μM) inhibited [ 3H]GABA release in a concentration-dependent manner with an EC 50 of 25 μM. This effect of kainate (30 μM) was prevented by the ion...

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Veröffentlicht in:European journal of pharmacology 1997-04, Vol.323 (2), p.167-172
Hauptverfasser: Cunha, Rodrigo A, Constantino, M.Dolores, Ribeiro, J.Alexandre
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creator Cunha, Rodrigo A
Constantino, M.Dolores
Ribeiro, J.Alexandre
description We studied the modulation of γ-aminobutyric acid (GABA) release by activation of kainate receptor in rat whole hippocampal synaptosomes. Kainate (10–300 μM) inhibited [ 3H]GABA release in a concentration-dependent manner with an EC 50 of 25 μM. This effect of kainate (30 μM) was prevented by the ionotropic non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM) and by the selective kainate receptor antagonist 5-nitro-6,7,8,9-tetrahydrobenzo( g)indole-2,3-dione-3-oxime (NS-102, 10 μM), but not by the selective non-competitive AMPA receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5 H-2,3-benzodiazepine (GYKI 52466, 100 μM). Other kainate receptor agonists, such as domoic acid (0.3–10 μM) and (2 S,4 R)-4-methylglutamic acid (MGA, 0.3–3 μM), also inhibited [ 3H]GABA release in a concentration-dependent manner with EC 50 values of 4.0 μM and 0.90 μM, respectively, whereas α-amino-3-hydroxy-5-methyl-4-oxazolepropionate (AMPA, 10–100 μM) was devoid of effect. These inhibitory effects of both domoic acid (3 μM) and MGA (1 μM) were antagonized by CNQX (10 μM). These results indicate that GABA release can be modulated directly by presynaptic high-affinity kainate heteroreceptors. © 1997 Elsevier Science B.V. All rights reserved.
doi_str_mv 10.1016/S0014-2999(97)00043-5
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Kainate (10–300 μM) inhibited [ 3H]GABA release in a concentration-dependent manner with an EC 50 of 25 μM. This effect of kainate (30 μM) was prevented by the ionotropic non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM) and by the selective kainate receptor antagonist 5-nitro-6,7,8,9-tetrahydrobenzo( g)indole-2,3-dione-3-oxime (NS-102, 10 μM), but not by the selective non-competitive AMPA receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5 H-2,3-benzodiazepine (GYKI 52466, 100 μM). Other kainate receptor agonists, such as domoic acid (0.3–10 μM) and (2 S,4 R)-4-methylglutamic acid (MGA, 0.3–3 μM), also inhibited [ 3H]GABA release in a concentration-dependent manner with EC 50 values of 4.0 μM and 0.90 μM, respectively, whereas α-amino-3-hydroxy-5-methyl-4-oxazolepropionate (AMPA, 10–100 μM) was devoid of effect. These inhibitory effects of both domoic acid (3 μM) and MGA (1 μM) were antagonized by CNQX (10 μM). These results indicate that GABA release can be modulated directly by presynaptic high-affinity kainate heteroreceptors. © 1997 Elsevier Science B.V. 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Kainate (10–300 μM) inhibited [ 3H]GABA release in a concentration-dependent manner with an EC 50 of 25 μM. This effect of kainate (30 μM) was prevented by the ionotropic non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM) and by the selective kainate receptor antagonist 5-nitro-6,7,8,9-tetrahydrobenzo( g)indole-2,3-dione-3-oxime (NS-102, 10 μM), but not by the selective non-competitive AMPA receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5 H-2,3-benzodiazepine (GYKI 52466, 100 μM). Other kainate receptor agonists, such as domoic acid (0.3–10 μM) and (2 S,4 R)-4-methylglutamic acid (MGA, 0.3–3 μM), also inhibited [ 3H]GABA release in a concentration-dependent manner with EC 50 values of 4.0 μM and 0.90 μM, respectively, whereas α-amino-3-hydroxy-5-methyl-4-oxazolepropionate (AMPA, 10–100 μM) was devoid of effect. These inhibitory effects of both domoic acid (3 μM) and MGA (1 μM) were antagonized by CNQX (10 μM). These results indicate that GABA release can be modulated directly by presynaptic high-affinity kainate heteroreceptors. © 1997 Elsevier Science B.V. All rights reserved.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Domoic acid</subject><subject>Excitatory Amino Acid Agonists - pharmacology</subject><subject>GABA (γ-aminobutyric acid) release</subject><subject>GABA Antagonists - pharmacology</subject><subject>Gabaergic and benzodiazepinic system</subject><subject>gamma-Aminobutyric Acid - metabolism</subject><subject>Glutamate</subject><subject>Glutamates - pharmacology</subject><subject>Hippocampus</subject><subject>Hippocampus - metabolism</subject><subject>Hippocampus - ultrastructure</subject><subject>In Vitro Techniques</subject><subject>Kainate</subject><subject>Kainic Acid - analogs &amp; derivatives</subject><subject>Kainic Acid - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Kainic Acid - drug effects</subject><subject>Synaptic Transmission - physiology</subject><subject>Synaptosome</subject><subject>Synaptosomes - metabolism</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2KFDEQgIMo6-zqIyzkIOIeWpN0fjonkUXdhQUP6kkkVNI1bLQ7aZOehXku38NnsueHue6poOqrH-oj5JKzt5xx_e4rY1w2wlr7xporxphsG_WErHhnbMMMF0_J6oQ8J-e1_logZYU6I2eWi65r1Yqk23QffZxjTjSv6Q_a3vz897eBMabsN_O2xEAhxJ4WHBAqUr-lvyEmmHFJBZzmXBZgjg-wnxETLTDT-zhNOcA4wUDrNsGC1TxifUGerWGo-PIYL8j3Tx-_Xd80d18-315_uGuCFGxuvLZdC4iiVT1Ypi1YaZBp2cnQaY-9NUb7NXgmhEc02vSdF5p5bgKXsm8vyOvD3KnkPxussxtjDTgMkDBvqjOdlVJZ9ijItVSyVTtQHcBQcq0F124qcYSydZy5nRC3F-J233bWuL0Qp5a-y-OCjR-xP3UdDSz1V8c61ADDukAKsZ4woVujxW79-wOGy9ceIhZXQ8QUsI-Lhtn1OT5yyH_pK6k2</recordid><startdate>19970404</startdate><enddate>19970404</enddate><creator>Cunha, Rodrigo A</creator><creator>Constantino, M.Dolores</creator><creator>Ribeiro, J.Alexandre</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>19970404</creationdate><title>Inhibition of [ 3H]γ-aminobutyric acid release by kainate receptor activation in rat hippocampal synaptosomes</title><author>Cunha, Rodrigo A ; Constantino, M.Dolores ; Ribeiro, J.Alexandre</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c420t-b6983aee235da9069a947e06484c86bed9776bfab022bee767d8b260b17c144d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Domoic acid</topic><topic>Excitatory Amino Acid Agonists - pharmacology</topic><topic>GABA (γ-aminobutyric acid) release</topic><topic>GABA Antagonists - pharmacology</topic><topic>Gabaergic and benzodiazepinic system</topic><topic>gamma-Aminobutyric Acid - metabolism</topic><topic>Glutamate</topic><topic>Glutamates - pharmacology</topic><topic>Hippocampus</topic><topic>Hippocampus - metabolism</topic><topic>Hippocampus - ultrastructure</topic><topic>In Vitro Techniques</topic><topic>Kainate</topic><topic>Kainic Acid - analogs &amp; derivatives</topic><topic>Kainic Acid - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, Kainic Acid - drug effects</topic><topic>Synaptic Transmission - physiology</topic><topic>Synaptosome</topic><topic>Synaptosomes - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cunha, Rodrigo A</creatorcontrib><creatorcontrib>Constantino, M.Dolores</creatorcontrib><creatorcontrib>Ribeiro, J.Alexandre</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cunha, Rodrigo A</au><au>Constantino, M.Dolores</au><au>Ribeiro, J.Alexandre</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of [ 3H]γ-aminobutyric acid release by kainate receptor activation in rat hippocampal synaptosomes</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>1997-04-04</date><risdate>1997</risdate><volume>323</volume><issue>2</issue><spage>167</spage><epage>172</epage><pages>167-172</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>We studied the modulation of γ-aminobutyric acid (GABA) release by activation of kainate receptor in rat whole hippocampal synaptosomes. Kainate (10–300 μM) inhibited [ 3H]GABA release in a concentration-dependent manner with an EC 50 of 25 μM. This effect of kainate (30 μM) was prevented by the ionotropic non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM) and by the selective kainate receptor antagonist 5-nitro-6,7,8,9-tetrahydrobenzo( g)indole-2,3-dione-3-oxime (NS-102, 10 μM), but not by the selective non-competitive AMPA receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5 H-2,3-benzodiazepine (GYKI 52466, 100 μM). Other kainate receptor agonists, such as domoic acid (0.3–10 μM) and (2 S,4 R)-4-methylglutamic acid (MGA, 0.3–3 μM), also inhibited [ 3H]GABA release in a concentration-dependent manner with EC 50 values of 4.0 μM and 0.90 μM, respectively, whereas α-amino-3-hydroxy-5-methyl-4-oxazolepropionate (AMPA, 10–100 μM) was devoid of effect. These inhibitory effects of both domoic acid (3 μM) and MGA (1 μM) were antagonized by CNQX (10 μM). These results indicate that GABA release can be modulated directly by presynaptic high-affinity kainate heteroreceptors. © 1997 Elsevier Science B.V. All rights reserved.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>9128835</pmid><doi>10.1016/S0014-2999(97)00043-5</doi><tpages>6</tpages></addata></record>
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subjects Animals
Biological and medical sciences
Domoic acid
Excitatory Amino Acid Agonists - pharmacology
GABA (γ-aminobutyric acid) release
GABA Antagonists - pharmacology
Gabaergic and benzodiazepinic system
gamma-Aminobutyric Acid - metabolism
Glutamate
Glutamates - pharmacology
Hippocampus
Hippocampus - metabolism
Hippocampus - ultrastructure
In Vitro Techniques
Kainate
Kainic Acid - analogs & derivatives
Kainic Acid - pharmacology
Male
Medical sciences
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Rats
Rats, Wistar
Receptors, Kainic Acid - drug effects
Synaptic Transmission - physiology
Synaptosome
Synaptosomes - metabolism
title Inhibition of [ 3H]γ-aminobutyric acid release by kainate receptor activation in rat hippocampal synaptosomes
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