Structure-activity and immunochemical data provide evidence of developmental- and tissue-specific myosuppressin signaling.
Structure-activity and immunochemical data provide evidence of developmental- and tissue-specific myosuppressin signaling.
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DOI：
10.1016/j.peptides.2012.05.002
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发表时间：
2012-08
期刊：
影响因子：
3
通讯作者：
Nichols R
中科院分区：
文献类型：
--
作者：
Dickerson M;McCormick J;Mispelon M;Paisley K;Nichols R
肌抑制素肽可显着减弱肠道和心脏的收缩。因此，描绘肌抑制素信号转导所涉及的机制可能有助于深入了解肌肉收缩性的肽能控制。研究果蝇肌抑制素（DMS、TDVDHVFLRFamide）结构-活性关系（SAR）以鉴定拮抗剂并探索信号传导。丙氨酰取代、N 端截短和修饰的氨基酸类似物确定了活性所需的残基和肽长度。免疫化学独立地提供了对肌抑制素机制的见解。 DMS 剂量依赖性地降低肠道蠕动和心肌收缩力；半最大响应时的不同有效浓度表明了组织特异性机制。替换天冬氨酸 2 (D2) 产生具有不同发育和组织特异性效应的类似物； [A2] DMS 在成虫肠道中模仿 DMS（100% 抑制），但仅使幼虫肠道收缩减少 32%，而在蛹心脏中的效力增加（126% 抑制）。 DMS 活性核心在不同发育阶段和组织中存在差异；成虫 (DHVFLRFamide) 和幼虫肠道 (TDVDHVFLRFamide)，以及成虫 (VFLRFamide) 和蛹心脏 (VFLRFamide)。用修饰的氨基酸对苯甲酰基苯丙氨酸取代 D2 和 D4，产生了发育和组织特异性拮抗剂。在存在蛋白酶抑制剂的情况下，与单独的肽或类似物相比，DMS 和 VFLRFamide 在成虫肠道中更有效，但在蛹心脏中较低或没有变化。 DMS 特异性抗血清对支配肠道或心脏的神经元进行染色。这项研究描述了新的拮抗剂和数据，以确定肌抑制素在肌肉生理学中多效性作用背后的发育和组织特异性机制。
Myosuppressin peptides dramatically diminish contractions of the gut and heart. Thus, delineating mechanisms involved in myosuppressin signaling may provide insight into peptidergic control of muscle contractility. Drosophila myosuppressin (DMS, TDVDHVFLRFamide) structure-activity relationship (SAR) was investigated to identify an antagonist and explore signaling. Alanyl-substituted, N-terminal truncated, and modified amino acid analogs identified residues and peptide length required for activity. Immunochemistry independently provided insight into myosuppressin mechanisms. DMS decreased gut motility and cardiac contractility dose dependently; the different effective concentrations at half maximal-response were indicative of tissue-specific mechanisms. Replacement of aspartic acid 2 (D2) generated an analog with different developmental- and tissue-specific effects; [A2] DMS mimicked DMS in adult gut (100% inhibition), yet decreased larval gut contractions by only 32% with increased potency in pupal heart (126% inhibition). The DMS active core differed across development and in tissues; adult (DHVFLRFamide) and larval gut (TDVDHVFLRFamide), and adult (VFLRFamide) and pupal heart (VFLRFamide). Substitution of D2 and D4 with a modified amino acid, p-benzoyl-phenylalanine, produced developmental-and tissue-specific antagonists. In the presence of protease inhibitors, DMS and VFLRFamide were more effective in adult gut, but lower or unchanged in pupal heart compared to peptide or analog alone, respectively. DMS-specific antisera stained neurons that innervated the gut or heart. This study describes novel antagonists and data to identify developmental- and tissue-specific mechanisms underlying the pleotropic effects of myosuppressin in muscle physiology.
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影响因子：
3
作者：
Duttlinger, A;Berry, K;Nichols, R
通讯作者：
Nichols, R
DOI：
10.1016/0006-291x(89)92512-6
发表时间：
1989-04-28
影响因子：
3.1
作者：
ROBB, S;PACKMAN, LC;EVANS, PD
通讯作者：
EVANS, PD
影响因子：
--
作者：
WANG, ZX;ORCHARD, I;LANGE, AB
通讯作者：
LANGE, AB
影响因子：
3
作者：
WANG, ZX;ORCHARD, I;LANGE, AB
通讯作者：
LANGE, AB
影响因子：
2.8
作者：
Stevens, J. S.;Cashman, C. R.;Dickinson, P. S.
通讯作者：
Dickinson, P. S.