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Research ArticleNEUROPHARMACOLOGY

Inhibition of Presynaptic Release-Facilitatory Kainate Autoreceptors by Extracellular Cyclic GMP

Chiara Cervetto, Guido Maura and Manuela Marcoli
Journal of Pharmacology and Experimental Therapeutics January 2010, 332 (1) 210-219; DOI: https://doi.org/10.1124/jpet.109.154955
Chiara Cervetto
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Guido Maura
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Manuela Marcoli
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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

  • 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.).

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.109.154955

  • 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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Journal of Pharmacology and Experimental Therapeutics: 332 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 332, Issue 1
1 Jan 2010
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Research ArticleNEUROPHARMACOLOGY

Inhibition of Presynaptic Release-Facilitatory Kainate Autoreceptors by Extracellular Cyclic GMP

Chiara Cervetto, Guido Maura and Manuela Marcoli
Journal of Pharmacology and Experimental Therapeutics January 1, 2010, 332 (1) 210-219; DOI: https://doi.org/10.1124/jpet.109.154955

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Research ArticleNEUROPHARMACOLOGY

Inhibition of Presynaptic Release-Facilitatory Kainate Autoreceptors by Extracellular Cyclic GMP

Chiara Cervetto, Guido Maura and Manuela Marcoli
Journal of Pharmacology and Experimental Therapeutics January 1, 2010, 332 (1) 210-219; DOI: https://doi.org/10.1124/jpet.109.154955
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