Functional couplings of the delta- and the kappa-opioid receptors with the G-protein-activated K+ channel.

The delta- and the kappa-opioid receptors were individually co-expressed with the G-protein-activated K+ (GIRK1) channel in Xenopus oocytes. Stimulation of these opioid receptors with selective agonists induced currents which were blocked by the opioid receptor antagonist naloxone. The current responses showed inward rectification and were blocked by 300 microM Ba2+, indicating that the effect of activated opioid receptors was mainly mediated by the GIRK1 channel. The EC50 value obtained from these responses was 45 nM for the agonist DPDPE in the oocytes injected with the delta-opioid receptor mRNA and the GIRK1 mRNA and 15 nM for the agonist U50488H in the oocytes injected with the kappa-opioid receptor mRNA and the GIRK1 mRNA. The Hill coefficient was 0.92 in the former and 0.93 in the latter. These results suggest that each of the delta- and the kappa-opioid receptors functionally couples with the GIRK1 channel.