Effect of opioid receptor agonists on nitric oxide synthase activity in rat cerebral cortex homogenate.

The effect of drugs acting at mu-, delta-, or kappa-opioid receptors on the activity of nitric oxide synthase (NOS) was determined in the cerebral cortex of the rat. The drugs included morphine and D-Ala2,Met,Phe4, Gly-ol5-enkephalin (DAMGO) (mu receptor), D-Ser2,Thr6-Leucine-enkephalin (DSTLE) and D-Pen2,D-Pen5-enkephalin (DPDPE) (delta receptor) and U-50, 488H (kappa receptor). As controls, two known inhibitors of NOS, NG-monomethyl-L-arginine (NMMA) and NG-nitro-L-arginine (NNA) were also included. The activity of NOS was determined by the rate of conversion of [3H]arginine into [3H]citrulline. NMMA and NNA inhibited the activity of NOS with IC50 values of 3.28 +/- 0.10 and 0.79 +/- 0.20 microM, respectively. DAMGO, DSTLE and DPDPE had no effect on the NOS activity. Morphine inhibited NOS activity by 25% at 10 mM concentration whereas the U-50,488H inhibited the NOS activity with an IC50 value of 107 microM. It is conclude that NNA is four time more potent than NMMA in inhibiting NOS activity whereas drugs acting at mu-, delta- and kappa- receptors have no direct action on central NOS activity in vitro.