title: Xendorphin B1, a novel opioid-like peptide determined from a Xenopus laevis brain cDNA library, produces opioid antinociception after spinal administration in amphibians.
abstract: Prodynorphins (PDYNs) from the African clawed frog (Xenopus laevis), originally described as 'proxendorphins', are novel members of the family of opioid-like precursor polypeptides and were recently discovered based on polymerase chain reaction (PCR) isolates from a Xenopus brain cDNA library. This amphibian prodynorphin was found in two isoforms, (Xen)PDYN-A and (Xen)PDYN-B, consisting of 247 and 279 amino acids, respectively. Each prepropeptide contains five potential opioid-like peptides, collectively named xendorphins. One of these, xendorphin B1 ((Xen)PDYN-B sequence 96-111: YGGFIRKPDKYKFLNA), is a hexadecapeptide that displaced [3H]naloxone and the radiolabelled kappa opioid, [3H]dynorphin A (1-17), with nanomolar affinity from rat brain membranes. Using the acetic acid pain test, the present study examined the antinociceptive effects of spinally administered xendorphin B1 in amphibians. Xendorphin B1 produced a long-lasting and dose-dependent antinociceptive effect in the Northern grass frog (Rana pipiens) with an ED50 value of 44.5 nmol/frog. The antinociceptive effects of xendorphin B1 were significantly blocked by pretreatment with the non-selective opioid antagonist, naltrexone. This is the first report of the in vivo characterization of a non-mammalian prodynorphin-derived peptide and suggests that xendorphin peptides may play a role in the modulation of noxious information in vertebrates.
authors.affiliation: Oklahoma State University-Center for Health Sciences, College of Osteopathic Medicine, Tulsa, OK, USA.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Stevens
authors.forename: Géza
authors.initials: G
authors.lastname: Tóth
authors.forename: Anna
authors.initials: A
authors.lastname: Borsodi
authors.forename: Sándor
authors.initials: S
authors.lastname: Benyhe
mesh_terms: D000663:Amphibians / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D015723:Gene Library; D009479:Neuropeptides / Q000235:genetics / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D018847:Opioid Peptides / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D036361:Peptide Hormones / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D011498:Protein Precursors / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D011894:Rana pipiens; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D029867:Xenopus Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D004745:Enkephalins; D009479:Neuropeptides; D018847:Opioid Peptides; D036361:Peptide Hormones; D011498:Protein Precursors; C481279:Xen-dorphin prohormone, Xenopus; D029867:Xenopus Proteins; C033660:preproenkephalin