Here we report the discovery, by high-throughput screening, of three novel (2-amino-5-keto)thiazole compounds that act as selective potentiators of nicotinic acetylcholine receptors. Compound selectivity was assessed at seven human nicotinic acetylcholine receptors (alpha1beta1gammadelta, alpha2beta4, alpha3beta2, alpha3beta4, alpha4beta2, alpha4beta4, and alpha7) expressed in mammalian cells o...

peripheral (autonomic and somatic) nervous systems. In the autonomic (sympathetic and parasympathetic) nervous system, acetylcholine is released from all preganglionic neurons, as well as from postganglionic parasympathetic neurons. Degradation of acetylcholine by the enzyme acetylcholinesterase occurs in the synapse between the presynaptic and postsynaptic membranes. There are two types of pos...

1. Acetylcholine (ACh) elicited depolarization and an increase in input conductance of the somatic muscle cells of the parasitic nematode Ascaris suum. 2. The relative potency of nicotinic and muscarinic agents was studied in this preparation. The order of potency of these compounds was metahydroxy-phenylpropyltrimethylammonium (HPPT) greater than 1.1 dimethyl-4-phenylpiperazinium (DMPP) greate...

Nicotinic acetylcholine receptors (nAChRs), members of the Cys-loop ligand-gated ion channels (LGICs) superfamily, are involved in signal transduction upon binding of the neurotransmitter acetylcholine or exogenous ligands, such as nicotine. nAChRs are pentameric assemblies of homologous subunits surrounding a central pore that gates cation flux, and are expressed at the neuromuscular junction ...

Emerging evidence suggests that the neurotransmitter acetylcholine (ACh) negatively regulates the development of the neuromuscular junction, but it is not clear if ACh exerts its effects exclusively through muscle ACh receptors (AChRs). Here, we used genetic methods to remove AChRs selectively from muscle. Similar to the effects of blocking ACh biosynthesis, eliminating postsynaptic AChRs incre...

The most commonly used antinematodal drugs in human and veterinary medicine are cholinergic agonists: imidazothiazole (praziquantel) tetrahydropyrimidines (pyrantel, morantel, and oxantel), quaternary/tertiary amines (bephenium and tribendimidine), pyridines (methyridine), and the amino-acetonitrile derivatives (AADs). These antiparasitic drugs produce spastic paralysis of the nematodes by sele...

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At the peripheral neuromuscular junction (NMJ), a significant number of nicotinic acetylcholine receptors (AChRs) recycle back into the postsynaptic membrane after internalization to intermingle with not-yet-internalized ;pre-existing' AChRs. However, the way in which these receptor pools are maintained and regulated at the NMJ in living animals remains unknown. Here, we demonstrate that recycl...

Bovine adrenal chromaffin cells have nicotinic acetylcholine receptors (AChRs) that mediate release of catecholamines from the cells in response to synaptic input, and resemble neuronal AChRs in pharmacology and antigenic profile. Results presented here show that a cAMP-dependent process enhances the function of adrenal chromaffin AChRs as a population in the plasma membrane. This was demonstra...