{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mitchell AJ"],"funding":["NIGMS NIH HHS","NIH HHS"],"pagination":["e68638"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3716696"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(7)"],"pubmed_abstract":["Substance P (SP) is a prototypical neuropeptide with roles in pain and inflammation. Numerous mechanisms regulate endogenous SP levels, including the differential expression of SP mRNA and the controlled secretion of SP from neurons. Proteolysis has long been suspected to regulate extracellular SP concentrations but data in support of this hypothesis is scarce. Here, we provide evidence that proteolysis controls SP levels in the spinal cord. Using peptidomics to detect and quantify endogenous SP fragments, we identify the primary SP cleavage site as the C-terminal side of the ninth residue of SP. If blocking this pathway increases SP levels, then proteolysis controls SP concentration. We performed a targeted chemical screen using spinal cord lysates as a proxy for the endogenous metabolic "],"journal":["PloS one"],"pubmed_title":["Proteolysis controls endogenous substance P levels."],"pmcid":["PMC3716696"],"funding_grant_id":["1DP2OD002374","GM007598","T32 GM007598","DP2 OD002374"],"pubmed_authors":["Lone AM","Mitchell AJ","Tinoco AD","Saghatelian A"],"additional_accession":[]},"is_claimable":false,"name":"Proteolysis controls endogenous substance P levels.","description":"Substance P (SP) is a prototypical neuropeptide with roles in pain and inflammation. Numerous mechanisms regulate endogenous SP levels, including the differential expression of SP mRNA and the controlled secretion of SP from neurons. Proteolysis has long been suspected to regulate extracellular SP concentrations but data in support of this hypothesis is scarce. Here, we provide evidence that proteolysis controls SP levels in the spinal cord. Using peptidomics to detect and quantify endogenous SP fragments, we identify the primary SP cleavage site as the C-terminal side of the ninth residue of SP. If blocking this pathway increases SP levels, then proteolysis controls SP concentration. We performed a targeted chemical screen using spinal cord lysates as a proxy for the endogenous metabolic ","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013","modification":"2025-04-04T22:07:21.94Z","creation":"2019-03-26T23:20:04Z"},"accession":"S-EPMC3716696","cross_references":{"pubmed":["23894327"],"doi":["10.1371/journal.pone.0068638"]}}