Glutamate receptors in the enteric nervous system: ionotropic or metabotropic?

Intracellular recording methods were used to investigate actions of glutama te on morphologically identified neurones in the myenteric and submucous pl exuses of guinea-pig small intestine. Glutamate evoked a tetrodotoxin-resis tant, slowly activating depolarizing response in most of the submucous neur ones (86 of 125, 69%) and a smaller number of myenteric neurones (6 of 60, 10%). The depolarizing responses were restricted to S-type neurones with un iaxonal morphology. The group I metabotropic glutamate receptor (mGluRs) ag onists quisqualate, 1S, 3R-ACPD and DHPG mimicked the depolarizing action o f glutamate. A group I mGluRs antagonist, S-4-carboxyphenylglycine (S-4CPG) , suppressed the glutamate responses with an IC50 of 357 mu M at 30 mu M gl utamate. Group II or III mGluRs agonists did not produce depolarizing respo nses and group II or III mGluRs antagonists did not alter glutamate-evoked depolarization. The ionotropic glutamate receptor (iGluRs) agonists NMDA, A MPA, or kainate did not evoke depolarizing responses and glutamate-evoked d epolarization was unaffected by the iGluRs antagonists D-APV, MK-801, or DN QX. No rapidly activating fast depolarizing responses reminiscent of fast e xcitatory postsynaptic potentials (EPSPs) were ever observed during applica tion of glutamate or AMPA and stimulus-evoked fast EPSPs were unaffected by DNQX. The results suggest that the excitatory action of glutamate on enter ic neurones is mediated by group I metabotropic glutamate receptors and tha t ionotropic glutamate receptors are not involved. The results also suggest that glutamate-mediated fast EPSPs may not be present in myenteric and sub mucous neurones in guinea-pig small bowel.