Kinetic properties of nitric oxide synthase in cerebral cortex and cerebellum of morphine tolerant mice

The effects of chronic morphine administration on the kinetics of nitric oxide synthase (NOS) activity were determined in the mouse cerebral cortex and cerebellum. Male Swiss-Webster mice were implanted subcutaneously with morphine pellets each containing 25 mg of morphine base for 3 days. Mice implanted with placebo pellets served as controls. NOS activity was determined by measuring the rate of conversion of [H-3]arginine to [H-3]citrulline. Morphine pellet implantation increased NOS activity in the cerebral cortex and cerebellum. Analysis of the Eadie-Hofstee plot indicated that the V-max of NOS in the cortex and cerebellum was 140 and 228 pmol [H-3]citrulline formed/min/mg protein and the K-m values were 9.3 and 10.1 mu mol/l, respectively. Mice implanted with morphine pellets had higher V-max values in both the cortex and cerebellum, but the K-m values did not differ from those of control mice implanted with placebo pellets. It is concluded that chronic treatment with morphine increases NOS activity in the brain without modifying its substrate affinity.