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谷氨酸受体与视皮层发育:促代谢型激动剂对环磷酸腺苷的影响

Glutamate receptors and development of the visual cortex: effect of metabotropic agonists on cAMP.

作者信息

Flavin H J, Daw N W, Gregory D S, Reid S N

机构信息

Department of Ophthalmology and Visual Science, Yale Medical School, New Haven, CT 06520-8061, USA.

出版信息

Prog Brain Res. 1996;108:263-72. doi: 10.1016/s0079-6123(08)62545-5.

Abstract

Glutamate receptors are more active in several respects in young animals than in adults. Here we examine the effect of metabotropic glutamate agonists on rat cortical cAMP during and after the critical period for visual cortex plasticity. Quisqualate produced a substantial increase in cAMP, which was larger during the critical period than in the adult. The increase was not affected by CNQX or APV, showing that it was not due to the action of quisqualate on ionotropic glutamate receptors. Both Type I mGluRs (mGluRs 1 and/or 5) and Type II mGluRs (mGluRs 2 and/or 3) probably contributed to the cAMP increase because (i) ACPD and L-CCG-I, which are more active on Type II mGluRs, were more effective than DHPG, which is more active on Type I mGluRs; and (ii) there was a significant difference in the effect of ACPD on the increase in cAMP, comparing mGluR1 knockout mice with control mice. Agonists which produce large stimulation of cAMP production (ACPD, L-CCG-I), as well as L-AP4, also produced small attenuations of forskolin-stimulated cAMP, but only at high concentrations. Thus, we conclude that it is the stimulation and/or potentiation of cAMP production that is significant, rather than the attenuation of forskolin-stimulated cAMP. Since this stimulation and/or potentiation is higher during the critical period than in the adult, and the cAMP second messenger system has been implicated in hippocampal plasticity, it may also play a role in visual cortex plasticity.

摘要

谷氨酸受体在幼龄动物的几个方面比成年动物更活跃。在这里,我们研究了代谢型谷氨酸受体激动剂在视觉皮层可塑性关键期及之后对大鼠皮层环磷酸腺苷(cAMP)的影响。喹啉酸导致cAMP大幅增加,在关键期比成年期增加幅度更大。这种增加不受CNQX或APV的影响,表明它不是由于喹啉酸对离子型谷氨酸受体的作用。I型代谢型谷氨酸受体(mGluRs 1和/或5)和II型代谢型谷氨酸受体(mGluRs 2和/或3)可能都对cAMP的增加有贡献,因为(i)对II型代谢型谷氨酸受体活性更高的ACPD和L-CCG-I比对I型代谢型谷氨酸受体活性更高的DHPG更有效;(ii)比较mGluR1基因敲除小鼠和对照小鼠时,ACPD对cAMP增加的影响存在显著差异。能大量刺激cAMP产生的激动剂(ACPD、L-CCG-I)以及L-AP4,也会在高浓度时对福斯高林刺激的cAMP产生轻微的减弱作用。因此,我们得出结论,重要的是cAMP产生的刺激和/或增强,而不是对福斯高林刺激的cAMP的减弱。由于这种刺激和/或增强在关键期比成年期更高,并且cAMP第二信使系统与海马可塑性有关,它可能也在视觉皮层可塑性中发挥作用。

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