Second messengers nitric oxide

Nitric Oxide. Nitric oxide [10102-43-9] NO, is a ubiquitous intracellular and intercellular messenger serving a variety of functions including vasodilation, cytotoxicity, neurotransmission, and neuromodulation (9). NO is a paramagnetic diatomic molecule that readily diffuses through aqueous and hpid compartments. Its locus of action is dictated by its chemical reactivity and the local environment. NO represents the first identified member of a series of gaseous second messengers that also includes CO. 

Guanylyl cyclases (GC) are a family of enzymes (EC 4.6.1.2) that catalyse the formation of the second messenger cyclic GMP (cGMP) from guanosine triphosphate (GTP). GCs are subdivided in soluble GCs and GCs that are membrane-bound and linked to a receptor. Activation occurs by nitric oxide (NO) and pqrtide hormones, respectively [1,2]. 

Finally, perhaps one of the oddest of recent discoveries is that toxic gases, such as nitric oxide (NO) and carbon monoxide (CO), can act as dual first/second messengers in the nervous system (Haley, 1998). Our current ideas of how drugs affect the complex events and regulation of synaptic neurotransmission are very simplistic and the real situation is obviously vastly more complicated. Some of these issues will be addressed in more detail in Chapter 14. 

Soluble forms of guanylyl cyclase are activated by nitric oxide 370 Nitric oxide functions as an intracellular second messenger 370... 

There are several mechanisms whereby antidepressants can modify intracellular events that occur proximal to the posts)maptic receptor sites. Most attention has been paid to the actions of antidepressants on those pathways that are controlled by receptor-coupled second messengers (such as cyclic AMP, inositol triphosphate, nitric oxide and calcium binding). However, it is also possible that chronic antidepressant treatment may affect those pathways that involve receptor interactions with protein tyrosine kinases, by increasing specific growth factor synthesis or by regulating the activity of proinflammatory cytokines. These pathways are particularly important because they control many aspects of neuronal function that ultimately underlie the ability of the brain to adapt and respond to pharmacological and environmental stimuli. One mechanism whereby antidepressants could increase the s)mthesis of trophic factors is... 

We have proposed a mechanism by which lL-1 exerts its deleterious effects on islet function and viability (Fig. 11 Corbett et al., 1992). In this proposed mechanism, lL-1 is released by macrophages during the initial stages of islet infiltration. IL-1 binds to a specific IL-1 receptors on the /3 cell activating a tyrosine kinase. Tyrosine kinase phosphorylation stimulates second messengers to induce the expression of c-/os, c-jun, the activation of NF-xB, and possibly other early transcriptional regulators. These early-immediate transcriptional response elements may activate or stimulate the expression of inducible nitric oxide... 

B. Nitric Oxide Effects on Intracellular Second Messengers... 

Neurons send electrical impulses from one part of the cell to another part of the same cell via their axons, but these electrical impulses do not jump directly to other neurons. Neurons communicate by one neuron hurling a chemical messenger, or neurotransmitter, at the receptors of a second neuron. This happens frequently, but not exclusively, at the sites of synaptic connections between them (Fig. 1 — 3). Communication between neurons is therefore chemical, not electrical. That is, an electrical impulse in the first neuron is converted to a chemical signal at the synapse between it and a second neuron, in a process known as chemical neurotransmission. This occurs predominantly in one direction, from the presynaptic axon terminal, to any of a variety of sites on a second postsynaptic neuron. However, it is increasingly apparent that the postsynaptic neuron can also talk back to the presynaptic neuron with chemical messengers of its own, perhaps such as the neurotransmitter nitric oxide. The frequency and extent of such cross-communication may determine how... 

Nitric oxide has major effects that are mediated by activation of cytoplasmic soluble guanylyl cyclase and stimulated production of cGMP, an important second messenger. In addition, nitric oxide can produce several reactive nitrogen derivatives by interaction with molecular oxygen and superoxide radicals (Table 19-2). These highly unstable molecules react with a variety of proteins, lipids, nucleic acids, and metals (especially iron) in cells (Davis, 2001). The remainder of this chapter discusses some of the second messenger-mediated effects of nitric oxide and the effects of inhibition of its production. 

This hemostatic/prothrombotic process is counterbalanced by vascular prostacyclin (PGl2) derived predominantly from COX-2 activity and nitric oxide (NO) released from endothelial cells. In vascular endothelial cells, COX-2 produces primarily PGI2 that inhibits platelet aggregation, induces vasodilation, inhibits the proliferation of vascular smooth-muscle cells, and is less susceptible to inhibition by low doses of aspirin. PGI2 and NO induce an intracellular increase of second messengers. NO inhibits platelet function by stimulation of a soluble guanylyl cyclase to produce cGMR... 

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