Phylogenesis of constitutively formed nitric oxide in non-mammals

It is widely recognized that nitric oxide (NO) in mammalian tissues is produced from L-arginine via catalysis by NO synthase (NOS) isoforms such as neuronal NOS (nNOS) and endothelial NOS (eNOS) that are constitutively expressed mainly in the central and peripheral nervous system and vascular endothelial cells, respectively. This review concentrates only on these constitutive NOS (cNOS) isoforms while excluding information about iNOS, which is induced mainly in macrophages upon stimulation by cytokines and polysaccharides. The NO signaling pathway plays a crucial role in the functional regulation of mammalian tissues and organs. Evidence has also been accumulated for the role of NO in invertebrates and non-mammalian vertebrates. Expression of nNOS in the brain and peripheral nervous system is widely determined by staining with NADPH (reduced nicotinamide adenine dinucleotide phosphate) diaphorase or NOS immunoreactivity, and functional roles of NO formed by nNOS are evidenced in the early phylogenetic stages (invertebrates and fishes). On the other hand, the endothelium mainly produces vasodilating prostanoids rather than NO or does not liberate endothelium-derived relaxing factor (EDRF) (fishes), and the ability of endothelial cells to liberate NO is observed later in phylogenetic stages (amphibians). This review article summarizes various types of interesting information obtained from lower organisms (invertebrates, fishes, amphibians, reptiles, and birds) about the properties and distribution of nNOS and eNOS and also the roles of NO produced by the cNOS as an important intercellular signaling molecule.