Cholinergic abnormalities, alongside senile plaques, neurofibrillary tangles, and extensive neuronal loss, are the major characteristics in Alzheimer's disease (AD). Both nicotinic and muscarinic acetylcholine receptors are decreased in AD, and it has been shown that the reduction in the number of acetylcholine receptors precedes other pathologic changes. Anti-cholinergic drugs induce amnesia, ...

Nicotinic receptors generally are presumed to consist of two alpha and three non-alpha subunits. We varied the relative levels of expression of the neuronal nicotinic alpha4 and beta2 receptor subunits in Xenopus laevis oocytes by nuclear injection of cDNAs coding for these subunits in alpha:beta ratios of 9:1, 1:1, and 1:9. The sensitivities of the receptors to acetylcholine and d-tubocurarine...

The flavonoid quercetin is a low molecular weight compound generally found in apple, gingko, tomato, onion and other red-colored fruits and vegetables. Like other flavonoids, quercetin has diverse pharmacological actions. However, relatively little is known about the influence of quercetin effects in the regulation of ligand-gated ion channels. Previously, we reported that quercetin regulates s...

More than 1 billion people around the world smoke, with 10 million cigarettes sold every minute. Cigarettes contain thousands of harmful chemicals including the psychoactive compound, nicotine. Nicotine addiction is initiated by the binding of nicotine to nicotinic acetylcholine receptors, ligand-gated cation channels activated by the endogenous neurotransmitter, acetylcholine. These receptors ...

Altered function of neuronal nicotinic acetylcholine receptors in the brain has recently been associated with an idiopathic form of partial epilepsy, suggesting that functional alterations of these receptors can be involved in the processes leading to epileptic seizures. Thus, nicotinic acetylcholine receptors may form a novel target for antiepileptic drug development. In the present study, var...

A kinetic scheme postulating the rapid formation of a partially active acetylcholine-receptor-drug complex from Xylocaine (or a derivative) and the active acetylcholine-receptor complex can account for the effects of Xylocaine and its derivatives at the neuromuscular junction. Transmembrane currents generated by an analogue computer programmed according to the scheme can exactly match end plate...

Mutations in ric-3 (resistant to inhibitors of cholinesterase) suppress the neuronal degenerations caused by a gain of function mutation in the Caenorhabditis elegans DEG-3 acetylcholine receptor. RIC-3 is a novel protein with two transmembrane domains and extensive coiled-coil domains. It is expressed in both muscles and neurons, and the protein is concentrated within the cell bodies. We demon...

M(2) muscarinic receptors on parasympathetic nerve endings inhibit acetylcholine release in the airways. In this study, the effects of dexamethasone on M(2) receptors in vivo and in primary cultures of airway parasympathetic neurons were tested. Treating guinea pigs with dexamethasone (0.1 mg/kg, daily for 2 d) substantially increased inhibitory M(2) muscarinic receptor function, decreasing air...

Signaling in the nervous system requires matching of neurotransmitter receptors with cognate neurotransmitters at synapses. The vertebrate neuromuscular junction is the best studied cholinergic synapse, but the mechanisms by which acetylcholine is matched with acetylcholine receptors are not fully understood. Because alterations in neuronal calcium spike activity alter transmitter specification...