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 isolated pancreas perfused with 2.8 mM glucose. L-Glutamate (3.10(-5)-10(-4)M) induced an immediate, transient and concentration-dependent glucagon release. The three non-N-methyl-D-aspartate (NMDA) receptor agonists, kainate (3.10(-5)-3.10(-3)M), alpha-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. Compared to glutamate, AMPA and quisqualate exhibited a similar efficacy, whereas kainate caused a 4-fold higher maximal glucagon response. In contrast, NMDA (10(-3)M) was ineffective. The selective antagonist of non-NMDA receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5.10(-5)M), totally prevented the glucagon response to 10(-4) M glutamate (IC50 congruent to 0.8 +/- 0.3 10(-6)M) and 3.10(-4)M kainate. Furthermore, quisqualate at a maximal effective concentration (3.10(-4)M) inhibited the response to kainate (10(-3)M). This study showed that L-glutamate stimulates glucagon release in rat pancreas by activating a receptor of the AMPA subtype.
Bertrand
G
G
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
Gross
R
R
Puech
R
R
Loubatières-Mariani
M M
MM
Bockaert
J
J
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D005934:Glucagon / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid / Q000187:drug effects*; D017470:Receptors, Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D011810:Quinoxalines; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D007051:Ibotenic Acid; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D005934:Glucagon; D007608:Kainic Acid