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

To investigate the G protein and protein kinase C (PKC) systems during the initial state of kappa-opioid tolerance, the low Km GTPase and PKC activities were measured following repeated treatment of rat with the kappa-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 Km 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 kappa-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.