Neuropeptidomics: Comparison of parallel reaction monitoring and data-independent acquisition for the analysis of neuropeptides using high-resolution mass spectrometry.

Targeted peptide quantitation by mass spectrometry is a rapidly emerging field. Traditionally it relied on the development and validation of multiple reaction monitoring assays that could comply with a high level of sensitivity, specificity, accuracy and reproducibility in complex biological samples. However, with the introduction of high-resolution mass spectrometers, other acquisition modes could provide more comprehensive datasets for identification and quantification but also for in-depth data mining.

Characterization of Substance P processing in mouse spinal cord S9 fractions using high-resolution Quadrupole-Orbitrap mass spectrometry.

Tachykinins are a family of pronociceptive neuropeptides with a specific role in pain and inflammation. Several mechanisms regulate endogenous tachykinins and Substance P (SP) levels, including the differential expression of protachykinin mRNA and the controlled secretion of tachykinins from neurons. Proteolysis is suspected to regulate extracellular SP concentrations but few studies were conducted on the metabolism of proneuropeptides and neuropeptides.

Tachykinins Processing is Significantly Impaired in PC1 and PC2 Mutant Mouse Spinal Cord S9 Fractions.

Substance P (SP) play a central role in nociceptive transmission and it is an agonist of the Neurokinin-1 receptor located in the lamina I of the spinal cord. SP is a major proteolytic product of the protachykinin-1 primarily synthesized in neurons. Proprotein convertases (PCs) are extensively expressed in the central nervous system and specifically cleave at C-terminal of either a pair of basic amino acids, or a single basic residue.