KAPPA-OPIOID RECEPTORS COUPLE TO INWARDLY RECTIFYING POTASSIUM CHANNELS WHEN COEXPRESSED BY XENOPUS OOCYTES

Xenopus oocytes expressed kappa-opioid specific binding sites after in jection 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 oo cytes that responded to the kappa agonist U-69593 by activating a larg e (1.0-1.5-mu A) K+ current. U-69593 exhibited an EC(50) of 260 +/- 50 nM and was blocked by the opioid antagonists norbinaltorphimine and n aloxone. 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 stimulat ion of inwardly rectifying K+ channels may be a potential effector mec hanism for kappa-opioid receptors.