Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substance P as a member of tachykinin family plays an important role in angiogenesis. Hemokinins (HKs) have been identified as new members of substance P-like peptides of tachykinin family. However, the effects of HKs on endothelial cells and angiogenesis have not been studied. For the first time, here we demonstrated that r/mHK-1, hHK-1 and hHK(4-11) dose-dependently stimulated the proliferation, migration, adhesion and tube formation of freshly isolated human umbilical vein endothelial cells (HUVECs), and further exhibited in vivo angiogenic effects in chick embryo chorioallantoic membrane model. The angiogenic effects of HKs were inhibited by the selective antagonist of neurokinin-1 rather than neurokinin-2 receptor. Mechanistically, HKs activated ERK1/2 phosphorylation, stimulated nitric oxide production, and upregulated the expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) in HUVECs. Taken together, our data suggest that HKs emerge as pivotal endogenous regulators of angiogenesis and represent potential targets for the intervention of angiogenesis in different pathological conditions given their specific peripheral distribution.
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PMID:Hemokinins modulate endothelium function and promote angiogenesis through neurokinin-1 receptor. 2255 85

Neurokinin B (NKB) is a potential regulator of pulsatile gonadotropin-releasing hormone (GnRH) secretion via activation of the neurokinin-3 receptor (NK3R). NKB with the consensus sequence of the tachykinin peptide family also binds to other tachykinin receptors [neurokinin-1 receptor (NK1R) and neurokinin-2 receptor (NK2R)] with low selectivity. In order to identify the structural requirements for the development of novel potent and selective NK3R agonists, a structure-activity relationship (SAR) study of [MePhe(7)]-NKB and other naturally occurring tachykinin peptides was performed. The substitutions to naturally occurring tachykinins with Asp and MePhe improved the receptor binding and agonistic activity for NK3R. The corresponding substitutions to NKB provided an NK3R selective analog.
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PMID:Structure-activity relationship study of tachykinin peptides for the development of novel neurokinin-3 receptor selective agonists. 2347 45


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