Mj. Barjavel et Hn. Bhargava, EFFECT OF OPIOID RECEPTOR AGONISTS ON NITRIC-OXIDE SYNTHASE ACTIVITY IN RAT CEREBRAL-CORTEX HOMOGENATE, Neuroscience letters, 181(1-2), 1994, pp. 27-30
The effect of drugs acting at mu-, delta-, or kappa-opioid receptors o
n the activity of nitric oxide synthase (NOS) was determined in the ce
rebral cortex of the rat. The drugs included morphine and D-Ala(2),Met
,Phe(4),Gly-ol(5)-enkephalin (DAMGO) (mu receptor), D-Ser(2),Thr(6)-Le
ucine-enkephalin (DSTLE) and D-Pen(2),D-Pen(5)-enkephalin (DPDPE) (del
ta receptor) and U-50, 488H (kappa receptor). As controls, two known i
nhibitors of NOS, N-G-monomethyl-L-arginine (NMMA) and N-G-nitro-L-arg
inine (NNA) were also included. The activity of NOS was determined by
the rate of conversion of [H-3]arginine into [H-3]citrulline. NMMA and
NNA inhibited the activity of NOS with IC50 values of 3.28 +/- 0.10 a
nd 0.79 +/- 0.20 mu M, respectively. DAMGO, DSTLE and DPDPE had no eff
ect 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 mu M. It is conclude that NNA is four time more
potent than NMMA in inhibiting NOS activity whereas drugs acting at m
u-, delta- and kappa-receptors have no direct action on central NOS ac
tivity in vitro.