Identification of dynorphins as endogenous ligands for an opioid receptor- like orphan receptor

S. Zhang, L. Yu

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

To identify the endogenous ligands for a cloned orphan receptor that shares high degrees of sequence homology with opioid receptors, this orphan receptor was expressed in Xenopus oocytes and in mammalian cell lines CHO-K1 and HEK-293. The coupling of the receptor to a G protein-activated K+ channel was used as a functional assay in oocytes. Endogenous opioid peptide dynorphins were found to activate the K+ channel by stimulating the orphan receptor. This activation was dose-dependent, with EC50 values at 45 and 37 nM for dynorphin A and dynorphin A-(1-13), respectively. The dynorphin effect was antagonized by the non-selective opioid antagonist naloxone but at rather high concentrations in the micromolar range. Naloxone also caused a rightward shift of the dose-response curve for dynorphin A, suggesting a competitive antagonism mechanism. In transiently transfected cells, 5 μM dynorphin A- (1-13) inhibited the forskolin-stimulated cyclic AMP increase by 51 and 35% in CHO-K1 and HEK-293 cells, respectively. Other classes of endogenous opioids, i.e. enkephalins and endorphins, caused very little activation of this receptor. These results suggest that this orphan receptor is a member of the opioid receptor family and that dynorphins are endogenous ligands for this receptor.

Original languageEnglish (US)
Pages (from-to)22772-22776
Number of pages5
JournalJournal of Biological Chemistry
Volume270
Issue number39
DOIs
StatePublished - 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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