Glutamate receptors of the AMPA type modulate neurotransmitter release andperistalsis in the guinea-pig isolated colon

To assess the role of AMPA and kainate receptors in modulating neurotransmi tter release from the myenteric plexus, the effect of alpha-amino-3-hydroxy -5-methyl-4-isoazole propionic ac id (AMPA) and kainic acid on endogenous a cetylcholine (ACh) and noradrenaline (NA) overflow from the guinea-pig isol ated colon was studied. AMPA inhibited spontaneous ACh overflow and increas ed electrically evoked NA overflow. Kainic acid did not influence both ACh and NA overflow. AMPA-mediated effects on ACh and NA overflow were signific antly reduced by the AMPA/kainate antagonist, 6-cyano-7-nitroquinoxalinc-2, 3-dione, CNQX. The inhibitory effect of AMPA on ACh overflow could be due, at least in part, to the AMPA-induced NA overflow as it was greatly reduced after adrenoceptor blockade and virtually abolished in sympathetically-den ervated animals. The possible functional significance of these findings was studied by measuring the efficiency of the peristaltic reflex in the prese nce of the different agonists. The efficiency of peristalsis was enhanced b y AMPA, whereas it was not modified by kainic acid. In conclusion, AMPA rec eptors, but not kainate receptors, may play a role in the modulation of ACh and NA release and of peristalsis in the guinea-pig colon. (C) 2000 Elsevi er Science Inc. All rights reserved.