Kappa-opioid receptors couple to inwardly rectifying potassium channels when coexpressed by Xenopus oocytes.
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.
Henry
D J
DJ
University of Washington, Department of Pharmacology, Seattle 98195.
Grandy
D K
DK
Lester
H A
HA
Davidson
N
N
Chavkin
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D044482:Benzeneacetamides; D001665:Binding Sites; D003001:Cloning, Molecular; D004594:Electrophysiology; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D008969:Molecular Sequence Data; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism* / Q000648:ultrastructure; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D018075:RNA, Complementary / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus
D044482:Benzeneacetamides; D015221:Potassium Channels; D011759:Pyrrolidines; D018075:RNA, Complementary; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D019204:GTP-Binding Proteins; C045444:U 69593