CA2+ CHANNEL INHIBITION BY KAPPA-OPIOID RECEPTORS EXPRESSED IN XENOPUS OOCYTES

FUNCTIONAL coupling between kappa opioid receptors and voltage-dependent Ca2+ channels was studied in the Xenopus oocyte translation system, in which specific RNAs encoding rat kappa opioid receptor, rabbit BI-2 alpha(1) subunit, and human beta subunit were co-injected. Perfusion of the oocytes with U50488H inhibited depolarization-evoked Ba2+ current (I-Ba) in a reversible manner, showing maximal inhibition of 25% at 1 mu M (IC50 = 31 nM). The inhibitory effect of U50488H was desensitized by pre-exposure of the oocytes to U50488H and abolished by the kappa opioid antagonist nor-binaltorphimine and by overnight pretreatment with pertussis toxin. Agents affecting the activity of protein kinase A or C did not affect the U50488H-induced inhibition of I-Ba. These findings suggest that kappa opioid receptors inhibit the activity of neuronal Ca2+ channels via GTP-binding proteins, without the participation of protein kinase A or C.