Acetylcholine receptor generation

Velazquez-Moctezuma, J., Shiromani, P. J. 8i Gillin, J. C. (1990b). Acetylcholine and acetylcholine receptor subtypes in REM sleep generation. Prog. Brain Res. 84,... 

An even simpler protocol for performing nucleophilic substitutions (aminations) and Suzuki reactions in one pot was reported by the Organ group for the generation of a 42-member library of styrene-based nicotinic acetylcholine receptor (nAChR) antagonists (Scheme 6.21) [49]. After considerable experimentation, the authors found that simultaneous nucleophilic displacement and Suzuki coupling could be carried out very effectively by charging the microwave process vessel with the palladium catalyst (0.5 mol% palladium-on-charcoal), the boronic acid [R1B(OH)2], the... 

Although NO does not itself use a G-protein for signalling, the mechanism of NO production in vascular endothelium is initiated by IP3 via a G-protein-linked acetylcholine receptor on the cell surface. The IP3 causes activation of nitric oxide synthase via calcium- calmodulin and the NO generated diffuses from the endothelial cell into the adjacent smooth muscle cell where cGMP is produced. 

Once the neurotransmitter is released from the presynaptic terminal it diffuses across the synaptic cleft. On the postsynaptic side it complexes with a membrane-bound macromolecule, its receptor. In synapses that have to generate action potentials within microseconds of neurotransmitter release, the receptors must be clustered in the postsynaptic membrane at high density, close to where the neurotransmitter is released. Such a synapse exists at the neuromuscular junction, where acetylcholine is the neurotransmitter. Acetylcholine is released from the presynaptic nerve terminal within 50 nm of the postsynaptic muscle membrane that contains densely arrayed acetylcholine receptors ( 10,000 acetylcholine rcccptors/pm2). There is a steady turnover of receptors, with newly synthesized receptors replacing those that are periodically degraded or not being utilized. 

Americ SP, William M (1995) Neuronal nicotinic acetylcholine receptors novel targets for CNS therapeutics. In Psychopharmacology the fourth generation of progress. Raven Press, New York, p 1001... 

Terry AV Jr, Gearhart DA, Mahadik SP, Warsi S, Waller JL. 2006. Chronic treatment with first or second generation antipsychotics in rodents Effects on high affinity nicotinic and muscarinic acetylcholine receptors in the brain. Neuroscience 140 1277-1287. 

Fig. 4 CHRNAl carries a 75-nt exon P3A. Its inclusion generates a nonfunctional alpha subunit of the acetylcholine receptor. hnRNP H and PTB silence recognition of exon PSA and induce its skipping. The IVS3-8G>A mutation identified in a patient with congenital myasthenic syndrome weakens the binding of hnRNP H and causes inclusion of exon PSA. Tannic add facilitates the expression of PTB and partially ameliorates aberrant spUcing due to IVS3-8G>A...

Zhang, Z.W., Coggan, J.S., and Berg, D.K., Synaptic currents generated by neuronal acetylcholine receptors sensitive to a-bungarotoxin. Neuron, 17, 1231, 1996. 

ABT-594 evolved from several years of research at Abbott Laboratories on nicotinic acetylcholine receptor modulators, directed initially toward treatment of Alzheimer s disease, and subsequently toward novel agents for treatment of pain. ABT-594 represents the first of a new generation of nAChR modulators to be tested as an analgesic agent in human clinical trials. The outcome of these studies with respect to both efficacy and... 

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