Abstract
Xenopus oocytes expressed kappa-opioid specific binding sites after injection of cRNA prepared from a clone of the rat kappa-opioid receptor. Coinjection of kappa receptor cRNA with cRNA coding for a G protein-linked, inwardly rectifying, K+ channel (GIRK1, or KGA) resulted in oocytes that responded to the kappa agonist U-69593 by activating a large (1.0-1.5-microA) K+ current. U-69593 exhibited an EC50 of 260 +/- 50 nM and was blocked by the opioid antagonists norbinaltorphimine and naloxone. The kappa agonist bremazocine was 200-fold more potent than U-69593 in eliciting K+ current but exhibited a partial agonist profile in this expression system. The present results indicate that stimulation of inwardly rectifying K+ channels may be a potential effector mechanism for kappa-opioid receptors.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Benzeneacetamides*
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Binding Sites
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Cloning, Molecular
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Electrophysiology
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Female
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism
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Ion Channel Gating / drug effects
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Molecular Sequence Data
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Naltrexone / analogs & derivatives
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Naltrexone / pharmacology
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Oocytes / metabolism*
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Oocytes / ultrastructure
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Potassium Channels / drug effects
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Potassium Channels / genetics
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Potassium Channels / metabolism*
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Pyrrolidines / pharmacology
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RNA, Complementary / administration & dosage
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RNA, Complementary / genetics
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Rats
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Receptors, Opioid, kappa / genetics
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Receptors, Opioid, kappa / metabolism*
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Xenopus
Substances
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Benzeneacetamides
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Potassium Channels
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Pyrrolidines
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RNA, Complementary
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Receptors, Opioid, kappa
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norbinaltorphimine
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Naltrexone
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GTP-Binding Proteins
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U 69593