G(Z) COUPLING TO THE RAT KAPPA-OPIOID RECEPTOR

We have expressed the cloned rat kappa-opioid receptor in human embryo nic kidney 293 cells and studied the ability of kappa-selective ligand s to inhibit adenylyl cyclase, In transfected 293 cells, activation of the kappa-opioid receptor by U50,488 and the dynorphins resulted in t he inhibition of cAMP accumulation. The inhibitory response was sensit ive to pertussis toxin and highly selective for kappa-agonists; neithe r mu- nor delta-opioids were able to activate the kappa-opioid recepto r, Upon co-transfection with the alpha subunit of G(z), inhibition of cAMP accumulation by kappa-agonist became refractory to pertussis toxi n, indicating that the kappa-opioid receptor can couple to both G(i) a nd G(z) proteins.