Novel Roles of Neuropeptide Processing Enzymes

EC3.4.24.15 in the Neurome

S. I. Kim, V. Grum-Tokars, Todd Swanson, E. J. Cotter, P. A. Cahill, J. L. Roberts, P. M. Cummins, Marc J. Glucksman

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Neuropeptide processing metalloenzymes, such as angiotensin converting enzyme, neprilysin, endothelin converting enzyme, neurolysin, and EC3.4.24.15 (EP24.15), are central to the formation and degradation of bioactive peptides. We present EP24.15 as a paradigm for novel functions ascribed to these enzymes in the neurome. Although the neurome typically encompasses proteomes of the brain and central nervous system, exciting new roles of these neuropeptidases have been demonstrated in other organ systems. We discuss the involvement of EP24.15 with clinical sequelae involving the use of gonadotropin-releasing hormone (GnRH; LHRH) analogs that act as enzyme inhibitors, in vascular physiology (blood pressure regulation), and in the hematologic system (immune surveillance). Hemodynamic forces, such as cyclic strain and shear stress, on vascular cells, induce an increase in EP24.15 transcription, suggesting that neuropeptidase-mediated hydrolysis of pressor/depressor peptides is likely regulated by changes in hemodynamic force and blood pressure. Lastly, EP24.15 regulates surface expression of major histocompatibility complex Class I proteins in vivo, suggesting that EP24.15 may play an important role in maintenance of immune privilege in sites of increased endogenous expression. In these extraneural systems, regulation of both neuropeptide and other peptide substrates by neuropeptidases indicates that the influence of these enzymes may be more global than was anticipated previously, and suggests that their attributed role as neuropeptidases underestimates their physiologic actions in the neural system.

Original languageEnglish (US)
Pages (from-to)456-467
Number of pages12
JournalJournal of Neuroscience Research
Volume74
Issue number3
DOIs
StatePublished - Nov 1 2003
Externally publishedYes

Fingerprint

Neuropeptides
Gonadotropin-Releasing Hormone
neurolysin
Peptides
Blood Vessels
Enzymes
Hemodynamics
Blood Pressure
Neprilysin
Enzyme Inhibitors
Peptidyl-Dipeptidase A
Proteome
Major Histocompatibility Complex
Immune System
Hydrolysis
Central Nervous System
Maintenance
Brain
Proteins

Keywords

  • GnRH
  • Hypertension
  • MHC Class I
  • Thimet oligopeptidase

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kim, S. I., Grum-Tokars, V., Swanson, T., Cotter, E. J., Cahill, P. A., Roberts, J. L., ... Glucksman, M. J. (2003). Novel Roles of Neuropeptide Processing Enzymes: EC3.4.24.15 in the Neurome. Journal of Neuroscience Research, 74(3), 456-467. https://doi.org/10.1002/jnr.10779

Novel Roles of Neuropeptide Processing Enzymes : EC3.4.24.15 in the Neurome. / Kim, S. I.; Grum-Tokars, V.; Swanson, Todd; Cotter, E. J.; Cahill, P. A.; Roberts, J. L.; Cummins, P. M.; Glucksman, Marc J.

In: Journal of Neuroscience Research, Vol. 74, No. 3, 01.11.2003, p. 456-467.

Research output: Contribution to journalArticle

Kim, SI, Grum-Tokars, V, Swanson, T, Cotter, EJ, Cahill, PA, Roberts, JL, Cummins, PM & Glucksman, MJ 2003, 'Novel Roles of Neuropeptide Processing Enzymes: EC3.4.24.15 in the Neurome', Journal of Neuroscience Research, vol. 74, no. 3, pp. 456-467. https://doi.org/10.1002/jnr.10779
Kim, S. I. ; Grum-Tokars, V. ; Swanson, Todd ; Cotter, E. J. ; Cahill, P. A. ; Roberts, J. L. ; Cummins, P. M. ; Glucksman, Marc J. / Novel Roles of Neuropeptide Processing Enzymes : EC3.4.24.15 in the Neurome. In: Journal of Neuroscience Research. 2003 ; Vol. 74, No. 3. pp. 456-467.
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