Inducible nitric oxide synthase and neuronal nitric oxide synthase (iNOS and nNOS)

Inducible nitric oxide synthase (iNOS, also called NOS2) and neuronal nitric oxide synthase (nNOS, also called NOS1) are two isoforms of the nitric oxide synthase enzyme family, responsible for catalyzing the conversion of L-arginine to nitric oxide (NO) and citrulline[3][4]. iNOS is primarily expressed in immune cells like macrophages and generates large amounts of NO as a defense response to inflammatory signals (such as cytokines and bacterial products), playing a key role in immune modulation and host defense but also contributing to inflammatory tissue damage and septic shock when dysregulated[1][4][6]. nNOS is constitutively expressed in neurons and select peripheral tissues, where it modulates synaptic signaling, neuroprotection, learning, memory, and central/peripheral neurotransmission and vascular tone; dysregulation of nNOS is implicated in neurodegenerative, psychiatric, and cardiovascular diseases[2][5][7]. Both enzymes require cofactors such as NADPH, FAD, FMN, heme, and tetrahydrobiopterin for activity, but they differ in regulation, with iNOS being calcium-independent after induction, while nNOS activity is regulated by calcium/calmodulin binding[3][4]. Selective inhibitors for each isoform are under investigation as therapeutics for pathologies driven by excessive or deficient NO signaling, but broad blockade carries safety risks due to NO’s pleiotropic physiological roles.

Other names

iNOS (NOS2)nNOS (NOS1)inducible NOSneuronal NOSNOS type II (for iNOS)NOS type I (for nNOS)

Inhibition of nitric oxide production by blocking L-arginine conversion; Inhibition of NO-mediated vasodilation; Suppression of immune cell-mediated NO response (iNOS); Modulation of synaptic signaling in CNS (nNOS)