Nitric oxide physiological action

Like nitric oxide, the discovery of the eicosanoid signalling molecules was a significant event in twentieth century physiology, due largely to research led by Sir John Vane (Nobel Prize 1982). The diverse actions of the eicosanoids include roles in muscle contraction, blood coagulation, salt and fluid homeostasis, inflammatory responses and pain sensitivity. 

Physiological sites proposed for nitric oxide action include the immune system, where nitric oxide acts as a cytostatic agent, is tumoricidal, and can inhibit viral replication. In the cardiovascular system, nitric oxide is the biological mediator of vasodilator responses to agents such as acetylcholine and bradykinin, which act as receptors on endothelial cells to activate NOS and stimulate nitric oxide production. Diffusible nitric oxide then activates guanylate cyclase in vascular smooth muscle cells, leading to the production of cyclic guano-sine monophosphate (GMP) and vasodilation. In the brain, stimulation of A-methyl-o-aspartate receptors on... 

Pro-inflammatory cytokines (see p. 432 et seq.) can also induce sleep, the effect depending on the concentration of the cytokine and the time of day. The effect on the sleep profile (increased non-REM and decreased REM sleep) appears to depend on the increased synthesis of prostaglandin D2 and nitric oxide which then alter the circadian rhythm. It is also known that some pro-inflammatory cytokines can affect the reuptake of 5-HT which plays an important role in regulating the sleep-wake profile. The endogenous fatty acid, oleamide, can cause sedation and induce sleep by activating cannabinoid receptors but also by potentiating the action of benzodiazepines on their receptor sites. Whether such action is of physiological relevance is presently unknown. 

Beckman, J. S., The physiological and pathological chemistry of nitric oxide, in Nitric Oxide Principles and Actions, Lancaster, J., Ed., Academic Press, San Diego, 1997,... 

The metabolic generation and fate of peroxynitrite remains an area of intense study with many complex reactions and interactions occurring. The physiological actions of nitric oxide and superoxide or peroxynitrite are leading to a reassessment of their individual and combined activities. 

NO is an important neuromodulator in the retina, and is implicated in many physiological processes (Goldstein et al., 1996). NO is synthesized from arginine via the action of nitric oxide synthase (NOS). Three distinct isoforms of NOS have been identified. Neuronal NOS (nNOS) and endothelial NOS (eNOS) are Ca -dependent. nNOS is constitutively expressed by certain types of amacrine cells in the retina. These cells often have long projections in the irmerplexiform layer (Sharma et al., 1997 Sharma et al., 2001). eNOS is expressed by the endothelial cells of blood vessels (Cheon et al., 2003). iNOS is Ca -independent and expressed in Muller and RPE cells in response to certain stimuli (Lopez-Costa et al., 1997). Activation of the NMDA receptor leads to an increase in intracellular calcium levels, which can induce expression of, and activate NOS isoforms, either directly (nNOS) or via the activation of calcium-dependent protein kinase C (PKC) (Lipton, 1999) (O Figure 3-6). 

Dawson VL, Dawson TM. 1995. Physiological and toxicological actions of nitric oxide in the central nervous system. Adv Pharmacol 34 323-342. 

Physiological and Toxicological Actions of Nitric Oxide in the Central Nervous System... 

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