Mohney R P, Zigmond R E
Department of Neurosciences, Case Western Reserve University, Cleveland Ohio 44106-4975, USA.
J Neurosci. 1998 Jul 15;18(14):5285-93. doi: 10.1523/JNEUROSCI.18-14-05285.1998.
Neurons in the adult rat superior cervical sympathetic ganglion (SCG) dramatically increase their content of vasoactive intestinal peptide (VIP) and its mRNA after axotomy in vivo and after explantation. Because the VIP gene contains a functional cAMP response element, the effects of cAMP-elevating agents on VIP expression were examined. VIP, forskolin, or isoproterenol increased cAMP accumulation in explanted ganglia. Secretin, a peptide chemically related to VIP, or forskolin increased VIP levels above those seen in ganglia cultured in control medium, whereas treatment with VIP or secretin increased the level of peptide histidine isoleucine (PHI), a peptide coded for by the same mRNA that encodes VIP. VIP or forskolin also increased VIP-PHI mRNA. In contrast, isoproterenol did not alter levels of VIP, PHI, or VIP-PHI mRNA. Although VIP or forskolin increased cAMP levels in both dissociated neurons and in non-neuronal cells, isoproterenol significantly stimulated cAMP accumulation only in the latter. VIP6-28 was an effective antagonist of the actions of exogenous VIP on cAMP and VIP-PHI mRNA in neuron-enriched cultures. When adult SCG explants were cultured in defined medium, endogenous VIP immunoreactivity was released. When VIP6-28 was added to such cultures, it significantly inhibited the increase in VIP-PHI mRNA that normally occurs. These data indicate that VIP, or a closely related molecule, produced by adult neurons after injury can enhance the expression of VIP. Such a mechanism may prolong the period during which VIP is elevated after axonal damage. The possibility is also discussed that, because VIP is present in preganglionic neurons in normal animals, its release during periods of increased sympathetic nerve activity could alter VIP expression in the SCG.
成年大鼠颈上神经节（SCG）中的神经元在体内轴突切断后以及离体培养后，其血管活性肠肽（VIP）及其mRNA的含量会显著增加。由于VIP基因含有一个功能性的cAMP反应元件，因此研究了提高cAMP的试剂对VIP表达的影响。VIP、福斯可林或异丙肾上腺素可增加离体神经节中cAMP的积累。促胰液素（一种与VIP化学结构相关的肽）或福斯可林可使VIP水平高于在对照培养基中培养的神经节中的水平，而用VIP或促胰液素处理可增加肽组氨酸异亮氨酸（PHI）的水平，PHI是由编码VIP的同一mRNA编码的一种肽。VIP或福斯可林也可增加VIP-PHI mRNA的水平。相比之下，异丙肾上腺素不会改变VIP、PHI或VIP-PHI mRNA的水平。尽管VIP或福斯可林可增加解离神经元和非神经元细胞中的cAMP水平，但异丙肾上腺素仅能显著刺激后者中cAMP的积累。VIP6-28是外源性VIP对富含神经元的培养物中cAMP和VIP-PHI mRNA作用的有效拮抗剂。当成年SCG外植体在限定培养基中培养时，内源性VIP免疫反应性会释放出来。当将VIP6-28添加到此类培养物中时，它可显著抑制正常情况下发生的VIP-PHI mRNA的增加。这些数据表明，成年神经元在损伤后产生的VIP或与之密切相关的分子可增强VIP的表达。这样一种机制可能会延长轴突损伤后VIP升高的时间。还讨论了一种可能性，即由于正常动物的节前神经元中存在VIP，其在交感神经活动增加期间的释放可能会改变SCG中VIP的表达。
