Reinitz C A, Herfel H G, Messinger L A, Stretton A O
Department of Zoology, University of Wisconsin-Madison, 1117 West Johnson Street, Madison, WI 53706, USA.
Mol Biochem Parasitol. 2000 Nov;111(1):185-97. doi: 10.1016/s0166-6851(00)00317-0.
Injection of Ascaris FMRFamide-like (AF) peptides and peptides encoded by genes in Caenorhabditis elegans were analyzed for effects on locomotion, body waveforms, and cAMP concentrations in adult female Ascaris suum. Injection of AF1 (KNEFIRFamide) or AF2 (KHEYLRFamide) inhibited the propagation of locomotory waves and reduced the number of waveforms, decreased the body length, and caused a large, long-lasting increase in cAMP. Muscle tissue was identified as a major source of the cAMP response induced by AF1. The AF1 analog AF1R6A did not affect cAMP levels by itself, but inhibited the cAMP response produced by AF1. AF8 (KSAYMRFamide) produced ventral coiling in the behavioral assay, and AF10 (GFGDEMSMPGVLRFamide) decreased the body length and increased the number of body waveforms. In dorsal muscle strips, AF10 produced a long-lasting contraction. Neither AF8 nor AF10 changed cAMP concentrations. AF17 (FDRDFMHFamide) increased body length and decreased cAMP. The neuropeptides encoded by C. elegans genes flp-4, flp-7, flp-9, and flp-13 produced paralysis and loss of waveforms, increased body length and, like AF17, decreased cAMP. Three new predicted peptides from C. elegans genome sequences were synthesized and tested. One produced ventral coiling but no change in cAMP; the other two gave no detectable responses. The fact that C. elegans neuropeptides produce behavioral and physiological effects in A. suum suggests that structurally related peptides may exist in A. suum. The profound changes in cAMP produced by some neuropeptides has important implications for understanding cAMP signaling and shows that neuropeptide-mediated signal transduction pathways are potential targets for anthelmintic drug development.
对猪蛔虫成虫注射蛔虫FMRF酰胺样（AF）肽以及秀丽隐杆线虫基因编码的肽，分析其对运动、身体波形和环磷酸腺苷（cAMP）浓度的影响。注射AF1（KNEFIRF酰胺）或AF2（KHEYLRF酰胺）会抑制运动波的传播，减少波形数量，缩短体长，并导致cAMP大幅持久增加。肌肉组织被确定为AF1诱导的cAMP反应的主要来源。AF1类似物AF1R6A本身不影响cAMP水平，但可抑制AF1产生的cAMP反应。AF8（KSAYMRF酰胺）在行为试验中引起腹侧卷曲，AF10（GFGDEMSMPGVLRF酰胺）缩短体长并增加身体波形数量。在背侧肌条中，AF10产生持久收缩。AF8和AF10均未改变cAMP浓度。AF17（FDRDFMHF酰胺）增加体长并降低cAMP。秀丽隐杆线虫基因flp - 4、flp - 7、flp - 9和flp - 13编码的神经肽会导致麻痹和波形消失，增加体长，并且与AF17一样降低cAMP。合成并测试了来自秀丽隐杆线虫基因组序列的三种新预测肽。一种引起腹侧卷曲但cAMP无变化；另外两种未检测到反应。秀丽隐杆线虫神经肽在猪蛔虫中产生行为和生理效应，这一事实表明猪蛔虫中可能存在结构相关的肽。一些神经肽引起的cAMP的深刻变化对于理解cAMP信号传导具有重要意义，并表明神经肽介导的信号转导途径是抗蠕虫药物开发的潜在靶点。
