Peptide fragments derived from the β-chain of hemoglobin (hemorphins) are centrally active in vivo

Thomas P. Davis, Terrence J. Gillespie, Frank Porreca

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


A novel tetrapeptide (hemorphin-4) and pentapeptide (hemorphin-5), derived from the β-chain of hemoglobin, were synthesized by solid-phase methodology, purified and the amino acid sequences confirmed. The central (ICV) effects of hemorphin-4 and -5 were studied in two models of phasic and tonic nociception, the mouse warm water tail-flick assay and hindpaw formalin assay, respectively. Additionally, two physiological endpoints, central modulation of bladder motility and central effects on intestinal propulsion, were studied in rats and mice, respectively. In the tail-flick assay, both peptides (40-100 nmoles) produced a dose-related naloxone-reversible antinociceptive effect when tested 10 min after peptide administration, with the tetrapeptide being slightly more potent than the pentapeptide. No effect was noted for either peptide using the tonic nociception assay, except at a dose of 150 nmoles for hemorphin-5. Inhibition of gastrointestinal propulsion was also not affected by either peptide. However, both peptides (10-40 nmoles) inhibited micturition contractions in a dose-related and naloxone-reversible fashion, with the tetrapeptide being twice as potent as the pentapeptide. These findings provide evidence that hemorphin-4 and -5 exert naloxone-reversible opioid actions in vivo and, therefore, may be physiologically important blood-borne peptides.

Original languageEnglish (US)
Pages (from-to)747-751
Number of pages5
Issue number4
StatePublished - 1989


  • FAB/MS
  • Hemoglobin
  • Hemorphins
  • Mu and delta receptors
  • Peptide fragments
  • Peptide metabolism
  • Peptide synthesis
  • Reflex contractions

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience


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