谷氨酸通过大鼠胰腺中AMPA亚型的兴奋性氨基酸受体刺激胰高血糖素分泌。

Glutamate stimulates glucagon secretion via an excitatory amino acid receptor of the AMPA subtype in rat pancreas.

作者信息

Bertrand G, Gross R, Puech R, Loubatières-Mariani M M, Bockaert J

机构信息

Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.

出版信息

Eur J Pharmacol. 1993 Jun 11;237(1):45-50. doi: 10.1016/0014-2999(93)90091-u.

DOI:10.1016/0014-2999(93)90091-u

PMID:7689469

Abstract

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.

摘要

研究了L-谷氨酸对用2.8 mM葡萄糖灌注的大鼠离体胰腺胰高血糖素分泌的影响。L-谷氨酸（3×10⁻⁵ - 10⁻⁴ M）诱导了即时、短暂且浓度依赖性的胰高血糖素释放。三种非N-甲基-D-天冬氨酸（NMDA）受体激动剂，即海人藻酸（3×10⁻⁵ - 3×10⁻³ M）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）（3×10⁻⁵ - 10⁻⁴ M）和喹啉酸（3×10⁻⁶ - 10⁻⁵ M），均引发了峰形的胰高血糖素反应。与谷氨酸相比，AMPA和喹啉酸表现出相似的效力，而海人藻酸引起的最大胰高血糖素反应高4倍。相比之下，NMDA（10⁻³ M）无效。非NMDA受体的选择性拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX；5×10⁻⁵ M）完全阻断了胰高血糖素对10⁻⁴ M谷氨酸（IC50约为0.8 ± 0.3×10⁻⁶ M）和3×10⁻⁴ M海人藻酸的反应。此外，最大有效浓度（3×10⁻⁴ M）的喹啉酸抑制了对海人藻酸（10⁻³ M）的反应。本研究表明，L-谷氨酸通过激活AMPA亚型受体刺激大鼠胰腺中的胰高血糖素释放。