加巴喷丁对蛋白激酶C或腺苷酸环化酶激活后大鼠三叉神经核谷氨酸释放促进作用的阻断。
Block by gabapentin of the facilitation of glutamate release from rat trigeminal nucleus following activation of protein kinase C or adenylyl cyclase.
作者信息
Maneuf Y P, McKnight A T
机构信息
Pfizer Global R&D, Cambridge Laboratories, University of Cambridge Forvie Site, Robinson Way, Cambridge CB2 2QB.
出版信息
Br J Pharmacol. 2001 Sep;134(2):237-40. doi: 10.1038/sj.bjp.0704227.
Abstract
The effect of activation of protein kinase C (PKC) or adenylyl cyclase on release of glutamate has been investigated in a perfused slice preparation from the rat caudal trigeminal nucleus. Stimulation of PKC by phorbol 12-myristate 13-acetate (PMA) produced a concentration-dependent increase in K(+)-evoked release of [(2)H]-glutamate (maximum increase 45%, EC(50) 11.8 nM), but in the presence of gabapentin (30 microM) the facilitation of release was blocked. The adenylyl cyclase activator forskolin (FSK) also induced a concentration-dependent increase in K(+)-evoked release of [(3)H]-glutamate (maximum increase 36%, EC(50) 2.4 microM), and again this facilitatory effect was blocked by gabapentin (30 microM). We suggest that these results may be of relevance to the antihyperalgesic properties of gabapentin, in conditions where concomitant release of substance P and CGRP produces activation of PKC and adenylyl cyclase respectively.
摘要
在大鼠尾侧三叉神经核的灌注切片标本中，研究了蛋白激酶C（PKC）或腺苷酸环化酶激活对谷氨酸释放的影响。佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）刺激PKC导致K⁺诱发的[²H]-谷氨酸释放呈浓度依赖性增加（最大增加45%，半数有效浓度[EC₅₀]为11.8 nM），但在加巴喷丁（30 μM）存在的情况下，释放的促进作用被阻断。腺苷酸环化酶激活剂福斯高林（FSK）也诱导K⁺诱发的[³H]-谷氨酸释放呈浓度依赖性增加（最大增加36%，EC₅₀为2.4 μM），并且这种促进作用同样被加巴喷丁（30 μM）阻断。我们认为，在P物质和降钙素基因相关肽伴随释放分别激活PKC和腺苷酸环化酶的情况下，这些结果可能与加巴喷丁的抗痛觉过敏特性相关。
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