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)

This study examines the contribution of tachykinins to the processes of inflammation. Neurokinin A (NKA), neurokinin B (NKB) and eledoisin (E) but not kassinin (K) have similar effects to substance P (SP) in priming neutrophils for increased superoxide anion (O2-) production in response to formyl-methionyl-leucyl-phenylalanine (FMLP). This similarity in activity may be due to the carboxy amino acid terminal end of these tachykinins being highly conserved. This was confirmed by demonstrating that SP fragment 7-11 (SP7-11) had the same priming effect as the whole molecule, whereas, the amino end fragment 1-4 (SP1-4) inhibited the response to FMLP. The priming effect of tachykinins was not confined to a single stimulus, such as FMLP, since NKA, NKB and SP also enhanced O2- production stimulated by platelet-activating factor (PAF), an important mediator of inflammation but a weak stimulus of O2- production on its own. In addition, all the tachykinins studied increased neutrophil antibody-dependent cell-mediated cytotoxicity (ADCC) towards opsonized target cells. In contrast to their effects on FMLP-induced O2- production, both SP fragments, SP1-4 and SP7-11, stimulated neutrophil ADCC and had a synergistic effect when used together.
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PMID:Activation of human neutrophils by tachykinins: effect on formyl-methionyl-leucyl-phenylalanine- and platelet-activating factor-stimulated superoxide anion production and antibody-dependent cell-mediated cytotoxicity. 768 58

The possibility that neuropeptides, in particular members of the tachykinin family are involved in inflammatory joint disease is widely disputed. Both clinical and experimental observations indicate that the tachykinin substance P (SP) may be involved in the pathogenesis of arthritis. We have studied the effects of tachykinins and the metabolites of SP on chondrocyte function. We have shown that the C-terminal pentapeptide sequence; H-Phe-Phe-Gly-Leu-Met-NH2 is biologically active in bovine chondrocyte cultures. The production of SP7-11 is limited by hydrolysis of the intact peptide by neutral endopeptidase (E.C. 3.4.24.11). The regulation of this enzyme would modulate the activity of substance P on articular cartilage chondrocytes.
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PMID:A metabolite of substance P, SP7-11 is involved in the pathogenesis of inflammatory joint disease. 768 13

Substance P belongs to the tachykinin family of neuropeptides which exhibit diverse pharmacological activity. The conformation of Phe1-Phe2-Gly3-Leu4-Met5-NH2 the C-terminal pentapeptide of substance P (SP7-11) has been studied by NMR and molecular dynamics (MD) methods. NMR studies were carried out both in DMSO-d6 and 95% H2O. Based on the observed chemical shifts, 3JNH alpha coupling constants, temperature coefficients of chemical shifts of NH resonances and the pattern of inter- and intraresidue NOE's, a predominantly extended backbone conformation has been deduced for the peptide in both DMSO and H2O. MD calculations carried out in vacuo indicate that the global minimum energy conformation of the molecule is folded with an intramolecular hydrogen bond between the protonated N-terminal and the C-terminal CONH2 group. The simulation shows that beta-turns are energetically unfavourable, while alpha-helices are seen to be unstable for the peptide. gamma-Bends at either Gly3 or Leu4 are the most preferred ones. Simulations carried out in DMSO as well as in water show a preference for a nearly extended conformation.
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PMID:NMR and molecular dynamics studies of tachykinins: conformation of the C-terminal pentapeptide of substance P(SP7-11). 959 24


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