Gluten exorphin B5 stimulates prolactin secretion through opioid receptors located outside the blood-brain barrier

Life Sci. 2005 Feb 25;76(15):1713-9. doi: 10.1016/j.lfs.2004.09.023. Epub 2004 Dec 20.


Gluten exorphin B5 (GE-B5) is a food-derived opioid peptide identified in digests of wheat gluten. We have recently shown that GE-B5 stimulates prolactin (PRL) secretion in rats; this effect is abolished by preadministration of the opioid receptor antagonist naloxone. However, since the structure of naloxone allows it to cross the blood-brain barrier (BBB) and antagonize opioid effects centrally as well as peripherally, it could not established, on the basis of those data, if GE-B5-induced PRL release is exerted through sites located inside or outside the BBB. In this study, we sought to determine the site of action of GE-B5 on PRL secretion, by pretreating male rats with naloxone methobromide (NMB), an opioid antagonist that does not cross the BBB. Four groups of rats were given the following treatments: 1) intravenous vehicle; 2) intravenous GE-B5 (3 mg kg(-1) body weight); 3) intraperitoneal NMB (5 mg kg(-1) body weight), followed by vehicle; 4) NMB, followed by GE-B5. Blood samples for PRL were taken at intervals for 40 minutes after vehicle or GE-B5 administration. GE-B5 stimulated PRL secretion; the effect was statistically significant at time 20. NMB preadministration completely abolished PRL response. Our experiment indicates that GE-B5 stimulates PRL secretion through opioid receptors located outside the BBB. Since opioid peptides do not exert their effect on PRL secretion directly, but via a reduced dopaminergic tone, our data suggest that GE-B5 can modify brain neurotransmitter release without crossing the BBB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier*
  • Male
  • Oligopeptides / pharmacology*
  • Oxymorphone / pharmacology
  • Prolactin / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Opioid / physiology*


  • Oligopeptides
  • Receptors, Opioid
  • exorphin B5
  • Prolactin
  • Oxymorphone