EVIDENCE FOR A GLUTAMATE RECEPTOR OF THE AMPA SUBTYPE WHICH MEDIATES INSULIN RELEASE FROM RAT PERFUSED PANCREAS
EVIDENCE FOR A GLUTAMATE RECEPTOR OF THE AMPA SUBTYPE WHICH MEDIATES INSULIN RELEASE FROM RAT PERFUSED PANCREAS
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DOI：
10.1111/j.1476-5381.1992.tb14340.x
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发表时间：
1992-06-01
影响因子：
7.3
通讯作者：
BOCKAERT, J
中科院分区：
文献类型：
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作者：
BERTRAND, G;GROSS, R;BOCKAERT, J
本文研究了l -谷氨酸对大鼠离体灌注胰腺胰岛素分泌的影响。所涉及的谷氨酸受体亚型已被确定。在轻度刺激的葡萄糖浓度（8.3 mM）存在下，l -谷氨酸(5 × 10（-5) - 4 × 10(-3) M）诱导了立即的、短暂的、浓度依赖性的胰岛素反应。另一方面，在非刺激性葡萄糖浓度（2.8 mM）下，l -谷氨酸（10(-3)M）不改变基础胰岛素分泌。3三种非nmda受体激动剂，kainate (10(-4) - 10(-3) M)， α -氨基-3-羟基-5-甲基-4-异氧唑丙酸(AMPA, 5 × 10（-5) - 10(-4) M）和quisqualate (5 × 10（-6) -5 × 10(-5) M）均引起胰腺灌注8.3 mm葡萄糖的短暂和浓度依赖性胰岛素反应。与谷氨酸相比，kainate表现出相似的疗效，而AMPA和quisqualate仅引起最大胰岛素反应低3倍。相反，NMDA (10（-4) - 10(-3) M）无效。非nmda受体拮抗剂6-氰-7-硝基喹啉-2,3-二酮（CNQX; 5 × 10(-5) M）完全阻止了l -谷氨酸（4 × 10(-4) M）和盐酸盐（2 × 10(-4) M）的刺激作用。相反，NMDA受体拮抗剂(+)-5-甲基-10,11-二氢- 5h -二苯并[a，d]环庚烯-5,10-亚胺（(+)MK801）没有效果。5 .谷氨酸（4 × 10(-4) M）的胰岛素分泌作用不受阿托品（3 × 10(-7) M）或河河鱼毒素（3 × 10(-6) M）的影响。6高最大有效浓度（4 × 10(-4) M）的准qualate抑制谷氨酸（10(-3)M）或海碱酸盐（4 × 10(-4) M）诱导的胰岛素释放。本研究表明，l -谷氨酸通过作用于AMPA亚型的兴奋性氨基酸受体，刺激大鼠胰腺胰岛素分泌。
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.