Xendorphin B1, a novel opioid-like peptide determined from a Xenopus laevis brain cDNA library, produces opioid antinociception after spinal administration in amphibians.
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.
Stevens
Craig W
CW
Oklahoma State University-Center for Health Sciences, College of Osteopathic Medicine, Tulsa, OK, USA.
Tóth
Géza
G
Borsodi
Anna
A
Benyhe
Sándor
S
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
D004745:Enkephalins; D009479:Neuropeptides; D018847:Opioid Peptides; D036361:Peptide Hormones; D011498:Protein Precursors; C481279:Xen-dorphin prohormone, Xenopus; D029867:Xenopus Proteins; C033660:preproenkephalin