Neurotransmitters applications

A departure from the catechol pattern of the natural neurotransmitters was achieved following application of the fact that arylsulfonamido hydrogens are nearly as acidic as phenolic OH groups. Nitration of p-benzyloxyacetophenone gave 18 which was reduced to 19 with Raney nickel and hydrazine, and in turn reacted with mesyl chloride to give sulfonamide 20. Methanesulfonate 20 was then transformed to soterenol (21), a clinically useful bronchodilator, in the... 

Serosal application of serotonin, a neurotransmitter localized histochemi-cally in the corneal nerves, increases the intracellular levels of cAMP, thereby elevating secretory flux of CE, which accounts for all the elevation in the corneal 7SC [119], The effect of serotonin on 7SC is slower than that of epinephrine, oc-... 

Intracerebroventricular infusion of CST-14 dramatically increases the amount of slow wave activity in rats, at the expense of wakefulness. The mechanism by which CST-14 enhances cortical synchronization has been established through the interaction of CST-14 with acetylcholine, a neurotransmitter known to be involved in the maintenance of cortical desynchronization. Application of acetylcholine (ACh) in the anesthetized animal increases fast activity, and this effect is blocked with the simultaneous addition of CST-14. These data suggest that CST-14 increases slow wave sleep by antagonizing the effects of ACh on cortical excitability. In addition to this mechanism, cortistatin may enhance cortical... 

The presence of specific receptors for the neurotransmitter on the postsynaptic membrane, such that application of the neurotransmitter to the synapse mimics the effects of presynaptic nerve stimulation... 

Capacitative Ca2+ entry is the predominant mode of regulated Ca2+ entry in nonexcitable cells but it also occurs in a number of excitable cell types. This pathway of Ca2+ entry is usually associated with the activation of phospholipase C, which mediates the formation of IP3 (see Ch. 20). Intracellular application of IP3 mimics the ability of hormones and neurotransmitters to activate calcium ion entry, and activation of calcium ion entry by hormones and neurotransmitters can be blocked by intracellular application of low-molecular-weight heparin, which potently antagonizes IP3 binding to its receptor. There is considerable evidence for the presence of an IP3 receptor in the plasma membrane of some cells types. 1(1,3,4,5)P4, a product of IP3 phosphorylation, has been shown in some cells to augment this action of IP3 in activating PM calcium ion entry, but in others IP3 alone is clearly sufficient. 

Direct application of neurotrophins to the brain of animals results in the rapid initiation of dramatic seizure activity, reflecting the coordinated discharge of large populations of neurons. This effect is the result of neurotrophin-stimulated release of neurotransmitters and enhanced synaptic efficiency. BDNF and NT3 cause... 

The first half of this century saw the beginning of a new era of medicine dominated by biochemistry. Various hormones and neurotransmitters were identified, synthesized and became available for research or medical applications. Several generations of behavioral endocrinologists have taken advantage of these breakthroughs to begin the tedious task of identifying the behavioral effects of hormones in humans and other animals (reviewed Becker, et al., 1992 Brown, 1994 Nelson, 1995). 

Several additional useful publications demonstrating practical applications of CE/MS methods for neurotransmitter analysis and neuropharmaceutical studies are those of Larsson and Lutz (2000) (neuropeptides including substance P) Hettiarachchi et al. (2001) (synthetic opioid peptides) Varesio et al. (2002) (amyloid-beta peptide) Zamfir and Peter-Katalinic (2004) (gangliosides) Peterson et al. (2002) (catecholamines and metanephrines) Cherkaoui and Veuthey (2002) (fluoxetine) and Smyth and Brooks (2004) (various lower molecular weight molecules including benzodiazepines, steroids, and cannabinols). 

Westerink BH, Damsma G, Rollema H, De Vries JB, Horn AS. 1987. Scope and limitations of in vivo brain dialysis a comparison of its application to various neurotransmitter systems. Life Sci 41(15) 1763-1776. 

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