Neurotransmitter, nitric oxide

A. J. Cunningham and J. B. Justice, Jr., Approaches to Voltammetric and Chromatographic Monitoring of Neurochemicals in Vivo, J. Chem. Ed. 1987, 64, A34. Another Nafion-coated electrode can detect 10 10 mol of the neurotransmitter nitric oxide within a single cell [T. Malinski and Z. Taha, Nitric Oxide Release from a Single Cell Measured in Situ by a Porphyrinic-Based Microsensor, Nature 1992, 358, 676]. 

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... 

Besides neuropeptides, nitric oxide is an inflammatory mediator in the airways, which is also a vasodilator and a neurotransmitter. Nitric oxide is produced by the enzymatic action of nitric oxide synthetase on L-arginine. Airways contain this enzyme in three different forms, two of which termed neuronal and endothelial nitric oxide synthetase are constitutive whereas the third form called inducible nitric oxide synthetase is inducible. The inflammatory cytokines including IL-1 and TNF-a augment the expression of inducible nitric oxide synthetase in human airway epithelial cells. Nitric oxide causes bronchodilation as a result of the relaxation of bronchial smooth muscles. It has also been suggested that nitric oxide is the neurotransmitter of the inhibitory NANC bronchodilation. The detrimental effects of nitric oxide include airway inflammation and vasodilation. It causes airway edema by increasing the erudition of plasma due to increased blood flow to postcapillary venules. The increased blood flow may also contribute to an increased mucus secretion. The role of nitric oxide in inflammatory responses has not yet been established. 

Erection occurs when adrenergic-induced sinusoid tone is antagonized by sacral parasympathetic stimulation that produces sinusoidal relaxation primarily by synthesis and release of the nonadrenergic-noncholinergic (NANC) neurotransmitter nitric oxide (NO). The contribution of acetylcholine-dependent release of NO from the vascular endothelium is uncertain. In vitro electrical stimulation of isolated corpus cavemosum strips (with or without endothelium) produces sinusoidal relaxation by release of neurotransmitters within nerve terminals that is resistant to adrenergic and cholinergic blockers. Inhibitors of the synthesis of NO or of guanosine monophosphate (GMP),... 

After an overview of neurotransmitter systems and function and a consideration of which substances can be classified as neurotransmitters, section A deals with their release, effects on neuronal excitability and receptor interaction. The synaptic physiology and pharmacology and possible brain function of each neurotransmitter is then covered in some detail (section B). Special attention is given to acetylcholine, glutamate, GABA, noradrenaline, dopamine, 5-hydroxytryptamine and the peptides but the purines, histamine, steroids and nitric oxide are not forgotten and there is a brief overview of appropriate basic pharmacology. 

NO is a gaseous neurotransmitter implicated in signaling in the central and peripheral nervous system as well as in the immune system and the vasculature. NO is formed from L-arginine by nitric oxide synthase (NOS). There are three isoforms of NOS. All isoforms require NADPH as a cofactor, use L-arginine as a substrate, and are inhibited by Nw-nitro-L-arginine methyl ester (L-NAME). The three isoforms are separate gene products. One isoform of NOS is a cytosolic, calcium/calmodulin-independent, inducible enzyme (iNOS). It is found in macrophages, neutrophils, vascular smooth muscle, and endothelia. The iNOS... 

Reiativeiy recentiy, the gases nitric oxide (NO) and carbon monoxide (CO) have been found to act as neurotransmitters in the nervous system. Nitric oxide is synthesized from L-arginine via nitric oxide synthase, requiring NADPH as a co-enzyme and tetrahydrobiopterin as a cofactor. Unlike other neurotransmitters, NO is a smaii, very soiubie moiecuie and cannot be stored in synaptic vesicles. Rather, it is synthesized on demand and freeiy diffuses through membranes. It is not broken down enzymaticaiiy because it is unstabie and degrades rapidiy. NO may have several actions, one of which is to increase the production of cGMP by guanyiyi... 

Penile erection occurs by relaxation of the smooth muscle of the corpus cavernosum, increasing blood flow into the penis and producing erection and rigidity. In a parallel fashion, vaginal pressure stimulation increases blood velocity and flow into clitoral arteries (Lavoisier et al. 1995). Cavernosal vasodilation is accomplished by neurotransmitters released from the cavernosal nerve and endothelial cells. One of the most important transmitters in this cascade is nitric oxide (NO), which induces synthesis of cyclic GMP from guanylate cyclase (Rajfer et al. 1992). Thus, ginkgo s vascular mechanisms could be responsible for some of the putative sexual effects. 

Opioids also interact with excitatory amino acid neurotransmitters. At lower micromolar concentrations, p agonists (e.g., DAMGO) enhance NMDA activity in the nucleus accumbens, but inhibit non-NMDA activity (Martin et al. 1997). At higher concentrations (5 pM), NMDA currents are reduced. Conversely, central administration of glutamate can precipitate a withdrawal syndrome in morphine-dependent animals, similar to the opioid antagonist naloxone. NMDA mechanisms also appear to be involved in the development of morphine tolerance. Competitive and noncompetitive NMDA antagonists and inhibitors of nitric oxide synthase reduce or eliminate tolerance to morphine (Elliott et al. 1995 Bilsky et al. 1996). However, this does not occur for tolerance to k opioids. Pharmacokinetics... 

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