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

The rat preprotachykinin I gene mRNA is alternatively spliced to yield three different mRNA species differing in their protein coding regions. We have produced recombinant vaccinia viruses expressing alpha-, beta-, and gamma-preprotachykinin to examine the tachykinin-related peptides produced upon post-translational processing of each individual precursor. Infection of BSC-40 or AtT-20 cell lines with a beta-preprotachykinin-encoding vaccinia virus recombinant results in the expression of the precursor protein. The pro-form (signal peptide removed) can be immunoprecipitated from extracts of infected cells. Infected cells of both types secrete into the culture medium a product(s) which reacts in radioimmunoassay with an antiserum shown to recognize precursor as well as mature substance P. Infected AtT-20, but not BSC-40, cells secrete into the culture medium a processed form(s) of beta-preprotachykinin which reacts in radioimmunoassay with an anti-serum which recognizes the amidated carboxyl terminus of substance P. The molecular nature of the tachykinin products produced in and secreted from AtT-20 cells infected with alpha-, beta-, and gamma-preprotachykinin-encoding recombinants was analyzed by combined high performance liquid chromatography and radioimmunoassay. Peptides were identified based on comigration with synthetic standards and antisera cross-reactivity. We determined that alpha-preprotachykinin is processed to the mature undecapeptide, substance P. beta-Preprotachykinin was processed into multiple products, including substance P, neurokinin A, neurokinin A(3-10), and neuropeptide K. gamma-Preprotachykinin was processed into substance P, neurokinin A, neurokinin A(3-10), and neuropeptide gamma. These five tachykinin peptide products were all routed through the regulated secretory pathway and were secreted into the medium in a cAMP-stimulatable fashion. Since all of these peptides have been shown to be biologically active, it is important to consider the biological consequences of their co-secretion in vivo.
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PMID:Multiple tachykinins are produced and secreted upon post-translational processing of the three substance P precursor proteins, alpha-, beta-, and gamma-preprotachykinin. Expression of the preprotachykinins in AtT-20 cells infected with vaccinia virus recombinants. 276 79

Human neurokinin-1 receptor cDNA was introduced into the pSFV1 Semliki Forest virus (SFV) vector and the in vitro transcribed RNA was electroporated into BHK cells with pSFV-Helper RNA. This procedure resulted in the packaging of a high-titer SFV-NK-1 virus stock containing approximately 5 x 10(9) infective units/ml. Infection of baby hamster kidney, COS-7, Chinese hamster ovary and human osteosarcoma cells yielded high levels of human neurokinin-1 receptor expression as assessed by [3H]substance P binding. The maximal receptor expression level obtained was 4 x 10(6) receptors/cell and studies of the post-infection time indicated that a high level of receptor expression was observed 10-24 h post-infection. The human neurokinin-1 receptor expressed in infected baby hamster kidney, COS-7 and Chinese hamster ovary cells was able to stimulate Ca2+ mobilization indicating functional coupling to guanine-nucleotide-binding proteins. The application of the Semliki Forest virus expression system will permit the rapid and efficient production of large quantities of receptor protein for both pharmacological and structural studies.
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PMID:High-level expression of the human neurokinin-1 receptor in mammalian cell lines using the Semliki Forest virus expression system. 752 21

The 1.3 S biotinylatable subunit of Proprionibacterium shermanii transcarboxylase complex was fused to the C-terminus of the human neurokinin 1 receptor gene and introduced into the Semliki Forest virus expression vector pSFV1. RNA transcribed from pSFV1-NK1-biot and pSFV-Helper2 was coelectroporated into BHK cells permitting in vivo packaging of recombinant virus. Infection of BHK and CHO cells with SFV-NK1-biot virus yielded high level of the fusion receptor as detected by metabolic labeling, immunoblotting with streptavidin alkaline phosphatase and binding to substance P. Like native receptor, the biotinylated receptor fusion was able to stimulate Ca2+ mobilization in infected CHO cells, indicating functional coupling to guanine-nucleotide-binding proteins.
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PMID:Functional activity of a biotinylated human neurokinin 1 receptor fusion expressed in the Semliki Forest virus system. 788 38

Bacillary dysentery arises when Shigella invades the colonic and rectal mucosae of the human gut and elicits a strong inflammatory response, which may lead to life-threatening complications. Hence, downregulation of the host inflammatory response is an appealing therapeutical alternative. The gastrointestinal tract is densely innervated, and nerve endings are often found in the vicinity of leukocytes. We have assessed the impact of experimental Shigella infection on levels of neuropeptides in the intestinal mucosa of rabbits. Ligated small intestinal loops were created in rabbits, and either live, pathogenic Shigella flexneri, a nonpathogenic mutant of Shigella, or NaCl was injected into the loops. Infection was allowed to proceed for 8 or 16 h, after which the rabbits were sacrificed and intestinal biopsies collected. Tissue destruction, fluid secretion and degree of bacterial invasion were monitored. Intestinal biopsies were homogenized, and levels of the neuropeptides calcitonin gene-related peptide, substance P, peptide YY (PYY), vasoactive intestinal peptide, somatostatin, galanin, motilin and neurotensin were measured by radioimmunoassay. Loops exposed to invasive Shigella had 5.7 times lower levels of PYY (P = 0.0095) than loops exposed to NaCl, after 16 h of infection. The levels of the other neuropeptides tested were unchanged. Inhibition of nicotinic cholinergic neurotransmission partly protected the intestinal mucosa from destruction elicited by invasive Shigella. These findings indicate that a tissue-invasive bacterium such as Shigella, which is strictly localized to the intestinal mucosa, activates intramural nerve reflexes that presumably involve a nicotinic synapse as well as the neuropeptide PYY.
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PMID:Neuromodulation of experimental Shigella infection reduces damage to the gut mucosa. 1502 12

Infection and inflammation of mucosal tissue may induce the production of neuropeptides, specifically Substance P and Neuropeptide Y. Since these neuropeptides are similar to antimicrobial peptides in their amino acid composition, amphipathic design, cationic charge, and size, we wanted to determine if they had antimicrobial activity against a panel of common bacteria and oral microorganisms using the radial diffusion assay. Neuropeptide Y and Substance P had antimicrobial activity against E. coli (MIC 20.6+/-5.5 microg/ml SEM and 71.5+/-15 SEM microg/ml, respectively), but did not have activity against laboratory strains of Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Serratia marcescens (MIC>500 microg/ml) nor oral strains of Streptococcus mutans, Candida albicans, and Actinobacillus actinomycetemcomitans (MIC>500 microg/ml). While Substance P and Neuropeptide Y did not have direct antimicrobial activity against the microorganisms tested, they still may stimulate local epithelial cells to produce other innate immune factors like defensins and cathelicidins. However, this remains to be determined.
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PMID:Antimicrobial activity of Substance P and Neuropeptide Y against laboratory strains of bacteria and oral microorganisms. 1680 79

Substance P (SP), acting on the neurokinin-1 receptor (NK-1R), is a neuropeptide, involved in the inflammatory processes. It promotes vasodilatation and increases vasopermeability, thus ensuing extravasation and accumulation of leucocytes at sites of injury. The aim of this study was to assess the impact of SP signalling on the responses during staphylococcal infection and the accompanying arthritis. Three experiments were performed where NK-1R-/- mice and controls were intravenously infected with different doses of Staphylococcus aureus. Clinical assessment of arthritis was performed as well as histological analysis of bone and cartilage destruction in the joints. In addition, the impact of NK-1R mutation on bacterial load in the kidneys as well as the phagocytic capacity of blood leucocytes were studied. Mice lacking the NK-1R displayed significantly higher bacterial load in the kidneys and significantly more severe synovitis and cartilage/bone destruction than the controls when inoculated with 1.4 x 10(7) staphylococci. Infection with 3.5 x 10(8) CFU/mouse induced sepsis. Thus, 11 days after bacterial inoculation 15 of 19 mice in the NK-1R-/- group had died versus 8 of 15 in the control group. Phagocytosis test revealed that significantly fewer macrophages from NK-1R-/- mice were able to phagocytose S. aureus when compared with macrophages from congenic control mice. Blocking the biological responses to substance P via its receptor NK-1R results in a less efficient clearance of bacteria leading to more severe arthritic lesions in mice.
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PMID:The impact of substance P signalling on the development of experimental staphylococcal sepsis and arthritis. 1822 12

BACKGROUND Infection and inflammatory diseases of the gut results in profound changes of intestinal motor function. Acute administration of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) was shown to have excitatory and neuromodulatory roles in the myenteric plexus. Here we aimed to study the effect of prolonged IL-1beta incubation on the response of myenteric neurones to different stimuli. METHODS Longitudinal muscle myenteric plexus preparations (LMMP's) of the guinea pig jejunum were incubated for 24 h in medium with or without IL-1beta. After loading with Fluo-4, calcium imaging was used to visualize activation of neurones. The response to application of serotonin (5-HT), substance P (SP) and ATP or to electrical fibre tract stimulation (eFTS) was tested. Expression of nNOS, HuD, calbindin and calretinin was compared by immunohistochemistry. KEY RESULTS IL-1beta concentration-dependently influenced the neuronal responsiveness and duration of the [Ca(2+)](i) rises to 5-HT and ATP, while it also affected the Ca(2+)-transient amplitudes induced by 5-HT, ATP and SP. Ca(2+)-transients in response to eFTS were observed in significantly more neurones per ganglion after IL-1beta (10(-10) and 10(-11) mol L(-1)). Peak [Ca(2+)](i) rise after eFTS was concentration-dependently decreased by IL-1beta. The duration of the [Ca(2+)](i) rise after eFTS was prolonged after IL-1beta 10(-12) mol L(-1). IL-1beta (10(-9) mol L(-1)) incubation did not affect the number of nNOS, calretinin and calbindin expressing neurones, nor did it induce neuronal loss (HuD). CONCLUSIONS & INFERENCES In this study, IL-1beta differentially modulates the neuronal response to eFTS and neurotransmitter application in the myenteric plexus of guinea pigs. This cytokine could be implicated in the motility disturbances observed during gastrointestinal inflammation.
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PMID:Prolonged IL-1beta exposure alters neurotransmitter and electrically induced Ca(2+) responses in the myenteric plexus. 1979 32