Enhancement of the rate of GTP hydrolysis in rat brain by repeated κ-opioid treatment

Abstract To investigate the G protein and protein kinase C (PKC) systems during the initial state of κ-opioid tolerance, the low K m GTPase and PKC activities were measured following repeated treatment of rat with the κ-agonist, U-50, 488. In behavioral studies, antinociceptive tolerance to U-50, 488 was developed following 7-day treatment with U-50, 488. Under these conditions, repeated administration of U-50, 488 significantly enhanced the basal low K m GTPase activity in the pons/medulla but not in the cortex and midbrain regions. On the other hand, repeated U-50, 488 treatment had no effect on PKC activity in cytosol and membrane fractions under the calcium-chelating conditions. These results indicate that repeated administration of κ-agonist, U-50, 488, increases in the basal hydrolysis of GTP to GDP in rat pons/medulla but not PKC activity which was observed in the case of repeated administration with morphine in rats.