Neuro transmission

To our knowledge no smdies have examined the effects of nitrites on GABA neuro transmission. However, when NO, the major mediator of the peripheral effects of nitrites, was administered within the paraventricular nucleus, it caused an increase in GABA concentrations (Horn et al. 1994). 

The administration of low doses of PCP to rodents induces hyperactivity and stereotypy (Chen et al. 1959 ). The observation that neuroleptics such as chlorpromazine, haloperidol, and pimozide, and adrenolytics such as alpha-methyl paratyrosine antagonize these behavioral effects of PCP suggests that they are mediated by facilitation of central dopaminergic neurotransmission (Murray and Horita 1979). The actions of PCP on central dopaminergic neurotransmission may be similar to amphetamine. A dose of PCP (2.5 mg/kg) in rats, which has no effects when given alone, enhances the behavioral effects of 1 and 3 mg/kg of d-amphetamine (Balster and Chait 1978). PCP, like dopamine, has also been shown to suppress plasma prolactin (Bayorh et al. 1983). However, the firm establishment of an excl usive relationship between dopamine neuro-transmission and PCP effects is difficult because of the prominent interactions of this drug with other neurotransmitter systems. 

Nonpeptide receptors Adenosine Aj Human cDNA Cardiac arrhythmia, asthma, myocardial ischemia, obesity, pain, renal disease, sleep apnea, stroke, cancer, inflammation, glaucoma, cystic fibrosis, Alzheimer s disease, Parkinson s disease Bradycardia, lipolysis inhibition, reduction of glomerular filtration and natriuresis, tubero-glomerular feedback, antinociception, renal vasodilatation-constriction, reduction of central cholinergic and noradrenergic nerve activity, presynaptic inhibition of excitatory neuro transmission... 

Julius Axelrod (USA), Ulf Von Euler (Sweden), Sir Bernard Katz (UK) (Nobel Prize, Medicine, 1979, synaptic neuro transmission, neuro transmitters) Erwin Neher Bert Sakmann (Germany, Nobel Prize, Physiology/ Medicine, 1991, patch-clamping ion channels)... 

Glutamate is a major excitatory neurotransmitter in the central nervous system. Theoretically, increased glutamater-gic neuro transmission may lead to excitatory neurotoxicity or exci to toxicity. The only two currently approved neuroprotective agents in the United States, riluzole for ALS and memantine for AD, may act to prevent glutamatergic excitotoxicity. 

Snyder, S.H. Wolosker, H. Blackshaw, S. Serine racemase a glial enzyme synthesizing D-serine to regulate glutamate-V-methyl-D-aspartate neuro-transmission. Proc. Natl. Acad. Sci. USA 1999, 96, 13,409-13,414. 

Wallmichrath I, Szabo B (2002b) Cannabinoids inhibit striatonigral GABAergic neuro transmission in the mouse. Neuroscience 113 671-682... 

Kaufer, D.. Friedman, A., and Soreq, H. (1999). Tlie vicious circle Long-lasting iranscriptional modulation of cholinergic neuro-transmission following stre.ss and ami-cholinesterase cxpo.sure. Neumscientist 5 173-183. 

The reactivation of AChE allows ACh to be hydrolyzed in the normal way, and therefore normal cholinergic neuro-transmission will resume. It is usually considered that the beneficial effects of oximes in OP poi.soning arc confined to peripheral nicotinic sites and that CNS effects are clinically insignificant (Bismuth etaL, 1992), although there is evidence that PAM can cross the blood-brain barrier (Sakurada etaL, 2003). This means that the beneficial effects will mainly be on neuromuscular transmission, and that there will be little action on parasympathetic effects, such as bronchoirhea, bronchoconstriction, and rhinorrhea, or on CNS effects. 

The small molecular dimensions of NO mean that it readily diffuses through cell walls. It acts as a messenger molecule in biological systems, and appears to have an active role in mammalian functions such as the regulation of blood pressure, muscle relaxation and neuro-transmission. A remarkable property exhibited by NO is that it appears to be cytotoxic (i.e. it is able to specifically destroy particular cells) and it affects the ability of the body s immune system to kill tumour cells. 

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