Kappa-opioid receptors couple to inwardly rectifying potassium channels when coexpressed by Xenopus oocytes

• Published in: Molecular pharmacology Vol. 47; no. 3; pp. 551 - 557
• Main Authors: Henry, D J, Grandy, D K, Lester, H A, Davidson, N, Chavkin, C
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.03.1995
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Benzeneacetamides; Binding Sites; Cloning, Molecular; Electrophysiology; Female; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; Ion Channel Gating - drug effects; Molecular Sequence Data; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Oocytes - metabolism; Oocytes - ultrastructure; Potassium Channels - drug effects; Potassium Channels - genetics; Potassium Channels - metabolism; Pyrrolidines - pharmacology; Rats; Receptors, Opioid, kappa - genetics; Receptors, Opioid, kappa - metabolism; RNA, Complementary - administration & dosage; RNA, Complementary - genetics; Xenopus
• ISSN: 0026-895X; 1521-0111

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.