Evidence for a glutamate receptor of the AMPA subtype which mediates insulin release from rat perfused pancreas.
1. The effect of L-glutamate has been studied on insulin secretion by the isolated perfused pancreas of the rat. The glutamate receptor subtype involved has been characterized. 2. In the presence of a slightly stimulating glucose concentration (8.3 mM), L-glutamate (5 x 10(-5)-4 x 10(-3) M) induced an immediate, transient and concentration-dependent insulin response. On the other hand, in the presence of a non stimulating glucose concentration (2.8 mM), L-glutamate (10(-3) M) did not modify the basal insulin secretion. 3. The three non-NMDA receptor agonists, kainate (10(-4)-10(-3) M), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 5 x 10(-5)-10(-4) M) and quisqualate (5 x 10(-6)-5 x 10(-5) M) all provoked a transient and concentration-dependent insulin response from pancreas perfused with 8.3 mM glucose. Compared with glutamate, kainate exhibited a similar efficacy, whereas AMPA and quisqualate elicited only a 3 fold lower maximal insulin response. In contrast, NMDA (10(-4)-10(-3) M) was ineffective. 4. An antagonist of non-NMDA receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5 x 10(-5) M) totally prevented the stimulatory effect of L-glutamate (4 x 10(-4) M) and kainate (2 x 10(-4) M). In contrast, the NMDA receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine ((+) MK801) was without effect. 5. The insulin secretory effect of glutamate (4 x 10(-4) M) was not affected by atropine (3 x 10(-7) M) or tetrodotoxin (3 x 10(-6) M). 6. Quisqualate at a high maximally effective concentration (4 x 10(-4) M) inhibited glutamate (10(-3) M) or kainate (4 x 10(-4) M)-induced insulin release. 7. This study shows that L-glutamate stimulates insulin secretion in rat pancreas, by acting on an excitatory amino acid receptor of the AMPA subtype.
Bertrand
G
G
Centre CNRS-INSERM de Pharmacologie-Endocrinologie UMR 6, 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; D001285:Atropine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D010179:Pancreas / Q000378:metabolism / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D007328:Insulin; D011810:Quinoxalines; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D018698:Glutamic Acid; D013779:Tetrodotoxin; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D001285:Atropine; D016318:Quisqualic Acid; D007608:Kainic Acid