Human RFamide-related peptide-1 diminishes cellular and integrated cardiac contractile performance.
Human RFamide-related peptide-1 diminishes cellular and integrated cardiac contractile performance.
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DOI：
10.1016/j.peptides.2010.07.012
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发表时间：
2010-11
期刊：
影响因子：
3
通讯作者：
Westfall MV
中科院分区：
文献类型：
--
作者：
Nichols R;Demers LA;Larsen BM;Robinson D;Converso K;Russell MW;Westfall MV
肽影响心功能不全，然而，收缩性能的肽能调节仍然相对不确定。我们发现了一种调节哺乳动物收缩性能的新型人类肽。FMRFamide相关肽（FaRP）家族的成员含有C-末端RF酰胺，但结构上不同的N-末端延伸。我们报告了人RFamide相关肽-1（hRFRP-1）和大鼠RFRP-1以剂量依赖性方式快速可逆地降低离体哺乳动物心肌细胞的缩短和舒张。哺乳动物的FaRP，26 RFa，结构上相关的RFRP-1只有一个RFamide没有影响心肌细胞的收缩功能。蛋白激酶C（PKC）抑制剂bisindolylmaleimide-1阻断hRFRP-1活性。用百日咳毒素（PTX）预处理并不减少hRFRP-1对收缩功能的影响。此外，小鼠静脉注射hRFRP-1可降低心率、每搏输出量、射血分数和心输出量。总的来说，这些发现与RFRP-1是一种内源性信号分子的结论是一致的，它激活PKC，并通过PTX不敏感的途径来调节心脏收缩功能。总之，hRFRP-1的这些负性变时性、变力性和负性效应是显著的;它们表明哺乳动物心脏中的直接急性细胞和器官水平反应。这是第一个已知的研究，以确定哺乳动物的FaRP与心脏功能的影响，开辟了一个新的研究领域的肽能调节收缩性能。从两栖动物到哺乳动物，RFRP结构高度保守，并且与无脊椎动物心脏抑制肽相似，表明RFRP-1参与重要的生理功能。阐明参与hRFRP-1合成、释放和信号传导的机制可能有助于开发预防或减轻心功能不全的策略。
Peptides influence cardiac dysfunction; however, peptidergic modulation of contractile performance remains relatively uncharacterized. We identified a novel human peptide that modulates mammalian contractile performance. Members of the FMRFamide-related peptide (FaRP) family contain a C-terminal RFamide but structurally variant N-terminal extension. We report human RFamide-related peptide-1 (hRFRP-1) and rat RFRP-1 rapidly and reversibly decreased shortening and relaxation in isolated mammalian cardiac myocytes in a dose dependent manner. The mammalian FaRP, 26RFa, structurally related to RFRP-1 by only an RFamide did not influence myocyte contractile function. The protein kinase C (PKC) inhibitor bisindolylmaleimide-1 blocked hRFRP-1 activity. Pretreatment with pertussis toxin (PTX) did not diminish hRFRP-1 influence on contractile function. In addition, intravenous injection of hRFRP-1 in mice decreased heart rate, stroke volume, ejection fraction, and cardiac output. Collectively these findings are consistent with the conclusion RFRP-1 is an endogenous signaling molecule that activates PKC and acts through a PTX-insensitive pathway to modulate cardiac contractile function. Taken together these negative chronotropic, inotropic, and lusitropic effects of hRFRP-1 are significant; they suggest direct acute cellular and organ-level responses in mammalian heart. This is the first known study to identify a mammalian FaRP with cardio-depressant effects, opening a new area of research on peptidergic modulation of contractile performance. The high degree of RFRP structure conservation from amphibians to mammals, and similarity to invertebrate cardioinhibitory peptides suggests RFRP-1 is involved in important physiological functions. Elucidation of mechanisms involved in hRFRP-1 synthesis, release, and signaling may aid the development of strategies to prevent or attenuate cardiac dysfunction.
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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：
4.8
作者：
Westfall, MV;Lee, AM;Robinson, DA
通讯作者：
Robinson, DA
影响因子：
--
作者：
BARNARD, CS;DOCKRAY, GJ
通讯作者：
DOCKRAY, GJ
影响因子：
2.9
作者：
Yano, T;Iijima, N;Ibata, Y
通讯作者：
Ibata, Y
影响因子：
21.3
作者：
Hinuma, S;Shintani, Y;Fujino, M
通讯作者：
Fujino, M