Detection of stable N-terminal protachykinin A immunoreactivity in human plasma and cerebrospinal fluid

Peptides. 2008 Jul;29(7):1201-6. doi: 10.1016/j.peptides.2008.02.006. Epub 2008 Feb 19.


Substance P (SP) is a neuropeptide that is released from sensory nerves and several types of immune cells. It is involved in the transmission of pain and has a number of pro-inflammatory effects. Like other neuropeptides, SP is derived from a large precursor peptide, protachykinin A (PTA). Alternative splicing results in the production of four distinct PTA molecules that all contain the sequence of SP and a common N-terminal region consisting of 37 amino acids. We have developed a sandwich immunoassay using antibodies against the N-terminal part of PTA. Here we demonstrate that N-terminal PTA immunoreactivity is present in human circulation and cerebrospinal fluid (CSF). The concentration was about 90 times higher in CSF than in EDTA-plasma. Analytical reversed phase HPLC revealed that NT-PTA 1-37 is the main immunoreactivity in human circulation and CSF. Moreover, compared to the low in vitro stability of SP of less than 12 min, NT-PTA immunoreactivity is absolutely stable in EDTA-plasma and CSF for more than 48 h. As NT-PTA 1-37 is produced in stoichiometric amounts and is theoretically co-released with SP, we suggest the measurement of NT-PTA immunoreactivity as surrogate molecule for the release of bioactive SP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Chelating Agents / metabolism
  • Chromatography, High Pressure Liquid
  • Drug Stability
  • Edetic Acid / blood
  • Humans
  • Immunoassay / methods*
  • Molecular Sequence Data
  • Protein Precursors / blood*
  • Protein Precursors / cerebrospinal fluid*
  • Protein Precursors / chemistry
  • Protein Precursors / immunology*
  • Tachykinins / blood*
  • Tachykinins / cerebrospinal fluid*
  • Tachykinins / chemistry
  • Tachykinins / immunology*
  • Time Factors


  • Chelating Agents
  • Protein Precursors
  • Tachykinins
  • protachykinin
  • Edetic Acid