Structure-activity studies of RFamide-related peptide-1 identify a functional receptor antagonist and novel cardiac myocyte signaling pathway involved in contractile performance.
Structure-activity studies of RFamide-related peptide-1 identify a functional receptor antagonist and novel cardiac myocyte signaling pathway involved in contractile performance.
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RFamide 相关肽-1 的结构活性研究确定了一种功能性受体拮抗剂和参与收缩性能的新型心肌细胞信号传导通路。
DOI：
10.1021/jm300760m
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发表时间：
2012
影响因子：
7.3
通讯作者：
Westfall,MargaretV
中科院分区：
文献类型：
--
作者：
Nichols,Ruthann;Bass,Chloe;Demers,Leslie;Larsen,Brian;Li,Elton;Blewett,Nathan;Converso-Baran,Kimber;Russell,MarkW;Westfall,MargaretV
Human RFamide-related peptide-1 (hRFRP-1, MPHSFANLPLRF-NH2) binds to neuropeptide FF receptor 2 (NPFF2R) to dramatically diminish cardiovascular performance. hRFRP-1 and its signaling pathway may provide targets to address cardiac dysfunction. Here, structure–activity relationship, transcript, Ca2+transient, and phospholabeling data indicate the presence of a hRFRP-1 pathway in cardiomyocytes. Alanyl-substituted and N-terminal truncated analogues identified that R11was essential for activity, hRFRP-1(8–12)mimicked hRFRP-1, and [A11]hRFRP-1(8–12)antagonized the effect of hRFRP-1 in cellular and integrated cardiac performance. RFRP and NPFF2R transcripts were amplified from cardiomyocytes and heart. Maintenance of the Ca2+transient when hRFRP-1 impaired myocyte shortening indicated the myofilament was its primary downstream target. Enhanced myofilament protein phosphorylation detected after hRFRP-1 treatment but absent in [A11]hRFRP-1(8–12)-treated cells was consistent with this result. Protein kinase C (PKC) but not PKA inhibitor diminished the influence of hRFRP-1 on the Ca2+transient. Molecules targeting this pathway may help address cardiovascular disease.
