GLUTAMATE STIMULATES GLUCAGON-SECRETION VIA AN EXCITATORY AMINO-ACID RECEPTOR OF THE AMPA SUBTYPE IN RAT PANCREAS

The effect of L-glutamate was studied on glucagon secretion from rat i solated pancreas perfused with 2.8 mM glucose. L-Glutamate (3.10(-5)-1 0(-4) M) induced an immediate, transient and concentration-dependent g lucagon release. The three non-N-methyl-D-aspartate (NMDA) receptor ag onists, kainate (3.10(-5)-3.10(-3) M), lpha-amino-3-hydroxy-5-methyl-4 -isoxazolepropionic acid (AMPA) (3.10(-5)-10(-4) M) and quisqualate (3 .10(-6)-10(-5) M), all elicited a peak-shaped glucagon response. Compa red to glutamate, AMPA and quisqualate exhibited a similar efficacy, w hereas kainate caused a 4-fold higher maximal glucagon response. In co ntrast, NMDA (10(-3) M) was ineffective. The selective antagonist of n on-NMDA receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5.10(-5 ) M), totally prevented the glucagon response to 10(-4) M glutamate (I C50 congruent-to 0.8 +/- 0.3 10(-6) M) and 3.10(-4) M kainate. Further more, quisqualate at a maximal effective concentration (3.10(-4) M) in hibited the response to kainate (10(-3) M). This study showed that L-g lutamate stimulates glucagon release in rat pancreas by activating a r eceptor of the AMPA subtype.