NICOTINAMIDE INHIBITS INDUCIBLE NITRIC-OXIDE SYNTHASE ENZYME-ACTIVITYIN MACROPHAGES BY ALLOWING NITRIC-OXIDE TO INHIBIT ITS OWN FORMATION

Nitric oxide (NO) production by macrophages is mainly regulated by ind uction of nitric oxide synthase (iNOS) by cytokines and microbial prod ucts. Nicotinamide (NIC) inhibits NO production by activated macrophag es in a dose dependent manner. NIC also inhibits NOS enzyme activity i n extracts from activated macrophages. The inhibition was noncompetiti ve with L-arginine (Ki 13.37 +/- 4.40 mM, n=3), uncompetitive versus N ADPH (Ki 3.06 +/- 0.17 mM, n=3) and tetrahydrobiopterin. Finally, the inhibition by nicotinamide was fully reversed by scavenging NO with he moglobin. We suggest that NIC acts by allowing NO to inhibit its own f ormation.