Mulderry P K
MRC Brain Metabolism Unit, University Department of Pharmacology, Edinburgh, Scotland, U.K.
Neuroscience. 1993 Mar;53(1):229-38. doi: 10.1016/0306-4522(93)90301-u.
There is a spontaneous induction of vasoactive intestinal polypeptide (VIP) expression in adult rat dorsal root ganglion sensory neurons when grown in culture. The mechanism of this induction may be the same as that responsible for the increased VIP expression in sensory neurons following peripheral axotomy in vivo. This study investigates the effects of depolarization and cyclic AMP on VIP expression (measured by radioimmunoassay) in cultures of newborn and adult rat sensory neurons. Unlike adult neurons, newborn rat sensory neurons, supported in culture with nerve growth factor, did not spontaneously express VIP. However, potassium-evoked depolarization and drugs that increase intracellular cyclic AMP concentrations (forskolin, 8-bromo cyclic AMP, isobutylmethylxanthine) interacted synergistically to stimulate high levels of VIP expression in newborn rat neurons. The contribution of depolarization to this effect could be mimicked by the L-type calcium channel agonist Bay K 8644 and blocked by the channel antagonist nifedipine, implying the involvement of calcium influx through L-type channels. While depolarization and forskolin individually had small effects on VIP content of adult rat sensory neuron cultures, there was no synergism of the kind seen in newborn rat cultures. Immunostaining showed that VIP was localized within approximately 30% of both newborn and adult rat sensory neurons. Thus, a subpopulation of newborn rat sensory neurons exhibit marked plasticity of VIP expression in an integrated response to activation of cyclic AMP- and calcium-dependent signalling pathways. This property is no longer present in mature neurons, however, where VIP expression is regulated by as yet undetermined factors.
成年大鼠背根神经节感觉神经元在体外培养时会自发诱导血管活性肠肽（VIP）表达。这种诱导机制可能与体内外周轴突切断后感觉神经元中VIP表达增加的机制相同。本研究调查了去极化和环磷酸腺苷对新生大鼠和成年大鼠感觉神经元培养物中VIP表达（通过放射免疫测定法测量）的影响。与成年神经元不同，在神经生长因子支持下进行培养的新生大鼠感觉神经元不会自发表达VIP。然而，钾离子诱发的去极化以及增加细胞内环磷酸腺苷浓度的药物（福斯可林、8-溴环磷酸腺苷、异丁基甲基黄嘌呤）协同作用，刺激新生大鼠神经元中高水平的VIP表达。去极化对这种效应的作用可被L型钙通道激动剂Bay K 8644模拟，并被通道拮抗剂硝苯地平阻断，这意味着通过L型通道的钙内流参与其中。虽然去极化和福斯可林单独对成年大鼠感觉神经元培养物中的VIP含量影响较小，但在新生大鼠培养物中未见这种协同作用。免疫染色显示，VIP定位于新生大鼠和成年大鼠约30%的感觉神经元内。因此，新生大鼠感觉神经元的一个亚群在对环磷酸腺苷和钙依赖性信号通路激活的综合反应中表现出VIP表达的显著可塑性。然而，在成熟神经元中不再存在这种特性，在成熟神经元中VIP表达受尚未确定的因素调节。
