The enterins:: A novel family of neuropeptides isolated from the enteric nervous system and CNS of Aplysia
The enterins:: A novel family of neuropeptides isolated from the enteric nervous system and CNS of Aplysia
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DOI：
10.1523/jneurosci.21-20-08247.2001
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发表时间：
2001-10-15
影响因子：
5.3
通讯作者：
Vilim, FS
中科院分区：
文献类型：
--
作者：
Furukawa, Y;Nakamaru, K;Vilim, FS
为了确定对海兔摄食系统具有广泛作用的神经肽，我们寻找在肠道和中枢神经系统中都存在的生物活性多肽。我们鉴定了一类存在于海兔肠道和中枢神经系统中的结构相关的非肽和十肽(肠肽)家族，其中大部分在C端具有HSFV酰胺序列。克隆得到的肠素前体的结构预测了20种不同肠段的35个拷贝。Northern分析、原位杂交和免疫细胞化学分析表明，肠蛋白在海兔的中枢和肠道中大量存在。利用基质辅助激光解吸/电离飞行时间质谱仪，我们表征了肠毒素前体的加工过程，证明了所有前体预测的肠肽都存在，并确定了各种肠肽的翻译后修饰。在肠道中发现了肠素阳性神经元胞体和突起，肠肽抑制了肠道的收缩。在中枢神经系统，控制摄食的大脑神经节和颊神经节含有肠管。肠蛋白也存在于连接这两个神经节的神经中。在喂养运动程序期间，肠素减少了中间神经元B4/5的放电。当直接测试B4/5的兴奋性时，这种肠毒素引起的放电减少也发生了。由于B4/5活性的降低对应于从摄食行为向摄食行为的转换，因此肠肽可能有助于这种程序转换。此外，由于肠素存在于整个神经系统，它们也可能在海兔的非摄食行为中发挥调节作用。
To identify neuropeptides that have a broad spectrum of actions on the feeding system of Aplysia, we searched for bioactive peptides that are present in both the gut and the CNS. We identified a family of structurally related nonapeptides and decapeptides (enterins) that are present in the gut and CNS of Aplysia, and most of which share the HSFVamide sequence at the C terminus. The structure of the enterin precursor deduced from cDNA cloning predicts 35 copies of 20 different enterins. Northern analysis, in situ hybridization, and immunocytochemistry show that the enterins are abundantly present in the CNS and the gut of Aplysia. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry we characterized the enterin-precursor processing, demonstrated that all of the precursor-predicted enterins are present, and determined posttranslational modifications of various enterins. Enterin-positive neuronal somata and processes were found in the gut, and enterins inhibited contractions of the gut. In the CNS, the cerebral and buccal ganglia, which control feeding, contained the enterins. Enterin was also present in the nerve that connects these two ganglia. Enterins reduced the firing of interneurons B4/5 during feeding motor programs. Such enterin-induced reduction of firing also occurred when excitability of B4/5 was tested directly. Because reduction of B4/5 activity corresponds to a switch from egestive to ingestive behaviors, enterin may contribute to such program switching. Furthermore, because enterins are present throughout the nervous system, they may also play a regulatory role in nonfeeding behaviors of Aplysia.