A subtype of κ-opioid receptor mediates inhibition of high-affinity GTPase inherent in Gi1 in Guinea pig cerebellar membranes

Hiroshi Ueda, Hidemi Misawa, Nobuyuki Fukushima, Toshiaki Katada, Michio Ui, Masamichi Satoh

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


The κ-opioid receptor agonists including U-50,488H and dynorphin A (1-17) in ranges of 0.1-100 nM inhibited the hydrolysis of GTP to GDP (Pi release) inherent in GTP-binding proteins (G proteins) in guinea pig cerebellar membranes. U-50,488H inhibited only high-affinity GTPase activity, not low-affinity activity. The action of this agonist was found to be biphasic, and there was no inhibition at concentrations >1 μM. The inhibition was abolished by pretreatment with preactivated pertussis toxin (PTX) at concentrations >1 μg/ml but not with preactivated cholera toxin (30 μg/ml). Similar blockade of κ-receptor-mediated inhibition was also observed when membranes were pretreated with a low concentration (8 μM) of N-ethylmaleimide (NEM) at low temperature (4°C), which alkylates the cysteine residue to be ADP-ribosylated by PTX; but this treatment caused no significant change in κ-agonist binding. When purified Gi1, but not Go, was reconstituted into membranes pretreated with NEM, the κ-receptor-mediated inhibition was recovered. These findings suggest that a subtype of κ-opioid receptor is coupled to inhibition of intrinsic activity of Gi1.

Original languageEnglish
Pages (from-to)845-851
Number of pages7
JournalJournal of Neurochemistry
Issue number2
Publication statusPublished - 1996 Feb
Externally publishedYes


  • Dynorphin
  • G protein
  • GTPase
  • Opioid κ-receptor
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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