title: Gluten exorphin B5 stimulates prolactin secretion through opioid receptors located outside the blood-brain barrier.
abstract: 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.
authors.affiliation: Dipartimento-Struttura Clinica Medica-Patologia Speciale Medica, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy. gfanciu@uniss.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fanciulli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dettori
authors.forename: Maria P
authors.initials: MP
authors.lastname: Demontis
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Tomasi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Anania
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Delitala
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010111:Oxymorphone / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000502:physiology*
chemical_list: D009842:Oligopeptides; D011957:Receptors, Opioid; C095012:exorphin B5; D011388:Prolactin; D010111:Oxymorphone