Cloning and characterization of Xen-dorphin prohormone from Xenopus laevis: A new opioid-like prohormone distinct from proenkephalin and prodynorphin

Patrick Pattee, Alina Elena Ilie, Sandor Benyhe, Geza Toth, Anna Borsodi, Srinivasa R. Nagalla

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Opioid-like peptides mediate analgesia and induce behavioral effects such as tolerance and dependence by ligand-receptor-mediated mechanisms. The classical opioid prohormones can generate several bioactive peptides, and these divergent families of prohormones share a common well conserved ancestral opioid motif (Tyr-Gly-Gly-Phe). Evidence from pharmacological and molecular cloning studies indicates the presence of multiple isoforms of opioid ligands and receptors that are as yet uncharacterized. To identify potential new members we used the opioid motif as an anchor sequence and isolated two distinct isoforms (Xen-dorphins A and B) of an opioid prohormone from Xenopus laevis brain cDNA library. Xen-dorphin prohormones can generate multiple novel opioid ligands distinct from the known members of this family. Both isoforms are present in a wide variety of tissues including the brain. Two potential bioactive peptides, Xen-dorphin-1A and -1B, that were chemically synthesized showed opioid agonist activity in frog and rat brain membranes using a [ 35S]GTPγS assay. Initial radioligand binding experiments demonstrated that Xen-dorphin-1B binds with high affinity to opioid receptor(s) and with potential preference to the kappa-opioid receptor subtype. Cloning of the Xen-dorphin prohormone provides new evidence for the potential presence of other members in the opioid peptide superfamily.

Original languageEnglish
Pages (from-to)53098-53104
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number52
DOIs
Publication statusPublished - Dec 26 2003

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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