PT  - JOURNAL ARTICLE
AU  - G H Ma
AU  - R J Miller
AU  - A Kuznetsov
AU  - L H Philipson
TI  - kappa-Opioid receptor activates an inwardly rectifying K+ channel by a G protein-linked mechanism: coexpression in Xenopus oocytes.
DP  - 1995 May 01
TA  - Molecular Pharmacology
PG  - 1035--1040
VI  - 47
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/47/5/1035.short
4100  - http://molpharm.aspetjournals.org/content/47/5/1035.full
SO  - Mol Pharmacol1995 May 01; 47
AB  - cRNAs encoding the kappa-opioid receptor and an inwardly rectifying, G protein-coupled, K+ channel were coinjected into Xenopus oocytes. The effects of kappa-opioid receptor agonists and antagonists on the membrane currents in these oocytes were studied using the two-electrode voltage-clamp technique. The kappa-opioid receptor agonists U69593 and dynorphin A induced a concentration-dependent inward current (EC50 of approximately 0.3 microM and approximately 30 nM, respectively) after coinjection of both cRNAs, whereas the mu-opioid receptor agonist [D-Ala2,N-MePhe4,Gly5-ol]enkephalin (10 microM) and the delta-opioid receptor agonist [D-Pen2,5]enkephalin (1 microM) had no effect. The agonist-induced inward current was reversible upon washing out of the agonists and was inhibited in the presence of the K+ channel blocker Ba2+ (0.1 mM). The specific kappa-opioid receptor antagonist norbinaltorphimine (0.1 microM) and the nonspecific opioid receptor antagonist naloxone (1 microM) abolished the agonist-induced currents. Furthermore, the agonist-induced currents exhibited rapid desensitization in the continuous presence of the agonists or after repeated application. Preincubation of the coinjected oocytes with pertussis toxin (400 ng/ml for 3 days of 1.5 microgram/ml for 24 hr) abolished most of the agonist-induced activation of the inwardly rectifying K+ current. We therefore conclude that specific stimulation of the kappa-opioid receptor can activate the inwardly rectifying K+ channel through a pertussis toxin-sensitive G protein.