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Evidence for a glutamate receptor of the AMPA subtype which mediates insulin release from rat perfused pancreas
Author(s) -
Bertrand G.,
Gross R.,
Puech R.,
LoubatièresMariani M.M.,
Bockaert J.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14340.x
Subject(s) - kainate receptor , ampa receptor , cnqx , medicine , nmda receptor , endocrinology , glutamate receptor , insulin , biology , chemistry , receptor
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 m m ), l ‐glutamate (5 × 10 −5 −4 × 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 m m ), 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 ), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA, 5 × 10 −5 −10 −4 m ) and quisqualate (5 × 10 −6 −5 × 10 −5 m ) all provoked a transient and concentration‐dependent insulin response from pancreas perfused with 8.3 m m 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 × 10 −5 m ) totally prevented the stimulatory effect of l ‐glutamate (4 × 10 −4 m ) and kainate (2 × 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 × 10 −4 m ) was not affected by atropine (3 × 10 −7 m ) or tetrodotoxin (3 × 10 −6 m ). 6 Quisqualate at a high maximally effective concentration (4 × 10 −4 m ) inhibited glutamate (10 −3 m ) or kainate (4 × 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.