Abstract
We found that both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate autoreceptors were present on the glutamate-releasing terminals of cerebellar parallel/climbing fibers and that they functioned as facilitatory autoreceptors. Extracellular cGMP inhibited the neurotransmitter release evoked by presynaptic kainate receptor activation; the inhibitory effect of extracellular cGMP was selective for the kainate autoreceptor-mediated response and did not affect the AMPA autoreceptor-mediated response. Endogenously synthesized cGMP might be the physiological source for the extracellular cGMP modulating the response to kainate autoreceptor activation.
Footnotes
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This study was supported by Italian Ministero dell'Istruzione, dell'Università e della Ricerca [Grant 2006058952-005] (to G.M.) and by University of Genoa, Progetto Ricerca Ateneo 2007 [Grant 020301002054] (to M.M.).
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.109.154955
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ABBREVIATIONS:
- AMPA
- α-amino-3-hydroxy-5-methyl-4-isoxazole propionate
- B
- basal
- 4-AP
- 4-aminopyridine
- ODQ
- 1H-[1,2,4]oxadiazole[4,3,-a]quinoxalin-1-one
- d-AP5
- d-(−)-2-amino-5-phosphonopentanoic acid
- GYKI 52466
- 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-(3-N-methylcarbamate)-2,3-benzodiazepine
- NMDA
- N-methyl-d-aspartate
- SNAP
- S-nitroso-penicillamine
- (S)-CPW 399
- (S)-α-amino-2,3,4,5,6,7-hexahydro-2,4-dioxo-1H-cyclopen tapyrimidine-1-propanoic acid
- CNQX
- 6-cyano-7-nitroquinoxaline-2,3-dione
- NS-102
- 5-nitro-6,7,8,9-tetrahydrobenzo-[g]-indole-2,3-dione-3-oxime
- GluR
- glutamate receptor.
- Received April 9, 2009.
- Accepted September 29, 2009.
- © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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Inhibition of Presynaptic Release-Facilitatory Kainate Autoreceptors by Extracellular Cyclic GMP
