Inhibition of presynaptic release-facilitatory kainate autoreceptors by extracellular cyclic GMP

J Pharmacol Exp Ther. 2010 Jan;332(1):210-9. doi: 10.1124/jpet.109.154955. Epub 2009 Sep 30.

Abstract

We found that both alpha-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspartic Acid / pharmacology
  • Autoreceptors / antagonists & inhibitors*
  • Cerebellum / metabolism
  • Cyclic GMP / metabolism
  • Cyclic GMP / physiology*
  • Dose-Response Relationship, Drug
  • Extracellular Space / metabolism*
  • Glutamic Acid / metabolism
  • In Vitro Techniques
  • Kainic Acid / pharmacology
  • Male
  • Presynaptic Terminals / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism
  • Receptors, Kainic Acid / antagonists & inhibitors*
  • Synaptosomes / metabolism

Substances

  • Autoreceptors
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Aspartic Acid
  • Glutamic Acid
  • Cyclic GMP
  • Kainic Acid