Hemopressin and other bioactive peptides from cytosolic proteins: are these non-classical neuropeptides?

Julia S. Gelman, Lloyd D. Fricker

Research output: Contribution to journalReview articlepeer-review

42 Scopus citations


Peptides perform many roles in cell-cell signaling; examples include neuropeptides, hormones, and growth factors. Although the vast majority of known neuropeptides are produced in the secretory pathway, a number of bioactive peptides are derived from cytosolic proteins. For example, the hemopressins are a family of peptides derived from alpha and beta hemoglobin which bind to the CB1 cannabinoid receptor, functioning as agonists or antagonists/inverse agonists depending on the size of the peptide. However, the finding that peptides derived from cytosolic proteins can affect receptors does not prove that these peptides are true endogenous signaling molecules. In order for the hemopressins and other peptides derived from cytosolic proteins to be considered neuropeptide-like signaling molecules, they must be synthesized in brain, they must be secreted in levels sufficient to produce effects, and either their synthesis or secretion should be regulated. If these criteria are met, we propose the name "non-classical neuropeptide" for this category of cytosolic bioactive peptide. This would be analogous to the non-classical neurotransmitters, such as nitric oxide and anandamide, which are not stored in secretory vesicles and released upon stimulation but are synthesized upon stimulation and constitutively released. We review some examples of cytosolic peptides from various protein precursors, describe potential mechanisms of their biosynthesis and secretion, and discuss the possibility that these peptides are signaling molecules in the brain, focusing on the criteria that these peptides would have to fill in order to be considered non-classical neuropeptides.

Original languageEnglish (US)
Pages (from-to)279-289
Number of pages11
JournalThe AAPS journal
Issue number3
StatePublished - Sep 2010
Externally publishedYes

ASJC Scopus subject areas

  • Pharmaceutical Science


Dive into the research topics of 'Hemopressin and other bioactive peptides from cytosolic proteins: are these non-classical neuropeptides?'. Together they form a unique fingerprint.

Cite this