Pituitary adenylate cyclase-activating polypeptide (PACAP) is an upstream regulator of prodynorphin mRNA expression in neurons
Pituitary adenylate cyclase-activating polypeptide (PACAP) is an upstream regulator of prodynorphin mRNA expression in neurons
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DOI：
10.1016/j.neulet.2010.08.044
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发表时间：
2010-11-05
影响因子：
2.5
通讯作者：
Tsuda, Masaaki
中科院分区：
文献类型：
--
作者：
Dong, Ying Xu;Fukuchi, Mamoru;Tsuda, Masaaki
虽然肌啡肽不仅广泛参与控制伤害性神经传递，而且还参与控制多种脑功能，如记忆和情绪，但目前还没有天然的调节因子可以诱导肌啡肽前体蛋白前肌啡肽（Pdyn） mRNA的表达。通过大鼠皮质神经元原代培养，我们发现垂体腺苷酸环化酶激活多肽（PACAP），血管活性肠多肽(VIP)/分泌素/胰高血糖素神经肽家族的成员，显著诱导Pdyn mRNA的表达。PACAP比VIP更有效，表明PAC1在PACAP诱导的Pdyn mRNA表达中起主要作用。Pdyn mRNA表达的增加与从头蛋白合成无关。腺苷酸环化酶/蛋白激酶A （PKA）激活剂forskolin诱导Pdyn mRNA表达，而蛋白激酶C （PKC）激活剂TPA不诱导Pdyn mRNA表达，提示PKA在其中起主要作用。加入PICA抑制剂H89后，pacap诱导的Pdyn mRNA表达受到抑制，这支持了PICA的参与。pacap诱导的NMDAR增强参与了Bdnf或c-fos mRNA的表达，而不参与Pdyn的表达。这些结果表明PACAP是通过PICA诱导Pdyn mRNA表达的上游调控因子。2010爱思唯尔爱尔兰有限公司版权所有。
Although dynorphins are widely involved in the control of not only nociceptive neurotransmission but also a variety of brain functions such as memory and emotion, no natural regulator for inducing the mRNA expression of prodynorphin (Pdyn), a precursor protein of dynorphins, is known. Using primary cultures of rat cortical neurons, we found that pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon neuropeptide family, markedly induces Pdyn mRNA expression. PACAP was much more effective than VIP, indicating a major role for PAC1 in the PACAP-induced Pdyn mRNA expression. The increase in Pdyn mRNA expression was independent of de novo protein synthesis. Administration of forskolin, an activator for adenylate cyclase/protein kinase A (PKA), but not TPA, an activator for protein kinase C (PKC), induced Pdyn mRNA expression, suggesting a major role for PKA. The involvement of PICA was supported by the inhibition of PACAP-induced Pdyn mRNA expression upon addition of H89, an inhibitor for PICA. The PACAP-induced potentiation of NMDAR was involved in the mRNA expression of Bdnf or c-fos but not Pdyn. These results suggest PACAP to be an upstream regulator for inducing Pdyn mRNA expression through PICA. (C) 2010 Elsevier Ireland Ltd. All rights reserved.