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)

Circulating monocytic cells may mediate neuroinvasion in transmissible spongiform encephalopathies by transporting prion protein (PrP) from sites of entry to the nervous system. Factors regulating monocyte-derived dendritic cell (DC) functions in neuronal tissue include neurogenic mediators, but their interactions with prion-infected DCs are unknown. Here, we report that neuropeptides regulate the interaction of DCs exposed to PrP(106-126). Inhibition of neurokinin-1-receptors activation with neurokinin-1-receptor antagonist or antibody attenuates substance P-induced enhancement of DC migration induced by PrP(106-126) and prion-protein-induced DC maturation. Other neuropeptides arrest chemotaxis. Data support a priming role of the neuropeptide substance P in PrP(106-126)-induced migration of DCs involving neurokinin-1-receptors.
 ...
PMID:Neurokinin-1 receptor interacts with PrP(106-126)-induced dendritic cell migration and maturation. 1558 49

Neuroinvasion of the enteric nervous system by prions is an important step in dissemination to the brain, yet very little is known about the basic process of enteric neuroinvasion. Using an alimentary model of neonatal disease transmission, neuroinvasion by scrapie prions in the ileum of lambs was detected by immunohistochemical staining for the disease-associated form of the prion protein, PrPSc. Odds ratios (OR) were determined for the frequency of PrPSc staining within enteric somata categorized by plexus location (myenteric, submucosal) and neurochemical staining (PGP 9.5, neural nitric oxide synthase, somatostatin, substance P, and vasoactive intestinal polypeptide). PrPSc was observed in 4.48 +/- 4.26% of myenteric neurons and 2.57 +/- 1.82% of submucosal neurons in five lambs aged 208-226 days but not in a lamb aged 138 days. The relative frequency of PrPSc within enteric somata was interdependent on plexus location and neurochemical type. Interestingly, PrPSc was observed more frequently within myenteric neurons than in submucosal neurons (PGP 9.5; OR = 1.72, 95% confidence interval = 1.21-2.44), and was observed within the myenteric plexus approximately 4x (2.16-6.94) more frequently in somatostatin neurons than in the general neural population stained by PGP 9.5. Nerve fibers stained for somatostatin were present in the mucosa and near PrPSc staining within Peyer's patches. The results suggest that somatostatin-expressing enteric neurons, with fiber projections near Peyer's patches, but with somata present in greatest proportion within the myenteric plexus, are an early target for neuroinvasion by scrapie prions and could serve an important role in neural dissemination.
 ...
PMID:Myenteric neurons of the ileum that express somatostatin are a target of prion neuroinvasion in an alimentary model of sheep scrapie. 1842 17

Prion diseases are characterized by accumulation of protease resistant isoforms of prion protein (PrP), and infiltration and activation of mononuclear phagocytes at the brain lesions. Interactions between prion proteins and immune cells during disease progression are still not very well understood. In the present study, multiwell chamber chemotaxis assay was carried out to assess the migratory response of macrophage cell line Ana-1 to a synthetic peptide homologous to residues 106-126 of the human prion protein. Specific protein kinase inhibitors were used to elucidate the signaling events underlying PrP106-126-induced macrophages migration, and a comparison with the signaling pattern of macrophage migration induced by substance P (SP) and N-formyl-methionyl-leucyl-phenylalanine (fMLP), respectively, was carried out. The results showed that PrP106-126 had a potent chemotactic effect on murine macrophage cell line Ana-1; that multiple signaling pathways might be involved in the PrP106-126-induced macrophage migrations; and that PrP106-126-induced chemotactic activity was similar to that induced by SP. These findings provide new insights into the mechanisms underlying the interaction between PrP and macrophages.
 ...
PMID:Induction of macrophage migration by neurotoxic prion protein fragment. 1944 1

The tachykinin neuropeptide, neurokinin B (NKB), belongs to a family of peptides having diverse roles in the brain. NKB, along with several other tachykinins, has been identified as a copper-binding peptide, however the physiological relevance of the binding is unclear. Previously, NKB was shown to limit the ability of copper to enter astrocytes and disrupt calcium homeostasis and it was thought that the peptide was sequestering the metal extracellularly. Here we use a fluorescein-labelled NKB peptide (F-NKB) to show that NKB is not retained extracellularly, but is endocytosed within 10-20min after addition to the cell media. The endocytosis is not inhibited when NKB is delivered as a copper-complex, [CuII(F-NKB)2]. Endocytosis of NKB can increase intracellular copper. Comparison to cells cultured in copper-free buffer indicated that apo-NKB can facilitate uptake of copper found in normal culture media. To achieve this NKB must compete with a variety of copper proteins, and we show that NKB can successfully compete with copper-binding peptides derived from the prion protein, itself associated with Cu(II) and Zn(II) metabolism. We suggest a mechanism of receptor mediated endocytosis to account for the observations.
 ...
PMID:Endocytosis of the tachykinin neuropeptide, neurokinin B, in astrocytes and its role in cellular copper uptake. 2694 44