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

To assess the role of AMPA and kainate receptors in modulating neurotransmitter release from the myenteric plexus, the effect of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainic acid on endogenous acetylcholine (ACh) and noradrenaline (NA) overflow from the guinea-pig isolated colon was studied. AMPA inhibited spontaneous ACh overflow and increased electrically-evoked NA overflow. Kainic acid did not influence both ACh and NA overflow. AMPA-mediated effects on ACh and NA overflow were significantly reduced by the AMPA/kainate antagonist, 6-cyano-7-nitroquinoxaline-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-denervated animals. The possible functional significance of these findings was studied by measuring the efficiency of the peristaltic reflex in the presence of the different agonists. The efficiency of peristalsis was enhanced by AMPA, whereas it was not modified by kainic acid. In conclusion, AMPA receptors, but not kainate receptors, may play a role in the modulation of ACh and NA release and of peristalsis in the guinea-pig colon.