Inagaki N, Kuromi H, Gonoi T, Okamoto Y, Ishida H, Seino Y, Kaneko T, Iwanaga T, Seino S
Division of Molecular Medicine, Chiba University School of Medicine, Japan.
FASEB J. 1995 May;9(8):686-91.
Although the excitatory amino acid glutamate and its receptors play crucial roles in many functions of the central nervous system (CNS), their presence in the peripheral tissues has remained unclear. In the present study, we have identified kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and N-methyl-D-aspartate (NMDA) receptor subtype mRNAs in pancreatic islets, using reverse transcriptase polymerase chain reaction (RT-PCR). Intracellular calcium ([Ca2+]i) measurements and electrophysiological recordings indicate that kainate, AMPA, and NMDA all elicit increases of [Ca2+]i in single pancreatic beta-cells and depolarize them. In addition, kainate and AMPA stimulate insulin secretion from isolated pancreatic islets, whereas NMDA does not. Also, immunocytochemical study shows the presence of intense glutaminase immunoreactivity in pancreatic alpha-cells and intrapancreatic ganglia, a finding compatible with the possibility that glutamate is released from alpha-cells as well as from neurons. Because the inhibitory amino acid gamma-amino butyric acid (GABA) is present in beta-cells as well as in neurons and inhibits glucagon secretion from alpha-cells, the present study suggests that glutamate and GABA are coordinated in the regulation of hormone secretion in pancreatic islets.
尽管兴奋性氨基酸谷氨酸及其受体在中枢神经系统（CNS）的许多功能中发挥着关键作用，但其在外周组织中的存在情况仍不清楚。在本研究中，我们利用逆转录聚合酶链反应（RT-PCR）在胰岛中鉴定出海藻酸、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和N-甲基-D-天冬氨酸（NMDA）受体亚型的mRNA。细胞内钙（[Ca2+]i）测量和电生理记录表明，海藻酸、AMPA和NMDA均可引起单个胰岛β细胞内[Ca2+]i升高并使其去极化。此外，海藻酸和AMPA可刺激分离的胰岛分泌胰岛素，而NMDA则无此作用。免疫细胞化学研究还显示，胰岛α细胞和胰腺内神经节中有强烈的谷氨酰胺酶免疫反应性，这一发现与谷氨酸可从α细胞以及神经元释放的可能性相符。由于抑制性氨基酸γ-氨基丁酸（GABA）存在于β细胞和神经元中，并抑制α细胞分泌胰高血糖素，因此本研究提示，谷氨酸和GABA在胰岛激素分泌调节中相互协调。
