Nicotine nicotinic acetylcholine receptor

Autoantibodies are directed against nicotinic acetylcholine receptors in myasthenia gravis, resulting in receptor loss, skeletal muscle paralysis, and dysfunction (100). In addition, antibodies directed against voltage-gated Ca " channels produce similar neuromuscular dysfunction of Lambert-Eaton... 

Curare is a generic term for various South American arrow poisons. Curare has been used for centuries by the Indians along the Amazon and Orinoco rivers for immobilizing and paralyzing wild animals used for food. Preparations of curare are derived from Strychnos species, which contain quaternary neuromuscular alkaloids like tubocurarine. Tubocurarine is a potent antagonist at the nicotinic acetylcholine receptor. 

Nicotinic receptors (nicotinic acetylcholine receptors, nACHR) exist not only in the membrane of vertebrate skeletal muscle at the synapse between nerve and muscle (muscle-type nAChR) but also at various synapses throughout the brain, mainly at presynaptic positions (neuronal-type nAChR). Whereas the muscle-type nAChR is precisely composed of two a 1-subunits, one (3 -subunit, one y -subunit and one y -subunit (adult)... 

Dajas-Bailador F, Wonnacott S (2004) Nicotinic acetylcholine receptors and the regulation of neuronal signalling. Trends Pharmacol Sci 25 317-324... 

Gotti C, Zoli M, Clementi F (2006) Brain nicotinic acetylcholine receptors native subtypes and their relevance. Trends Pharmacol Sci 27 482-491... 

Jensen AA, Frolund B, Liljefors T et al (2005) Neuronal nicotinic acetylcholine receptors structural revelations, target identifications, and therapeutic inspirations. J Med Chem 48 4705—4745... 

Karlin A (2002) Emerging structure of the nicotinic acetylcholine receptors. Nat Rev Neurosci 3 102-114... 

Unwin N (2003) Structure and action of the nicotinic acetylcholine receptor explored by electron microscopy. FEES Lett 555 91-95... 

The open channel has in most cases a selective permeability, allowing a restricted class of ions to flow,for example Na+, K+, Ca++ or Cl- and, accordingly, these channels are called Na+-channels, K+-channels, Ca -channels and Cr-channels. In contrast, cation-permeable channels with little selectivity reject all anions but discriminate little among small cations. Little is known about the structures and functions of these non-selective cation channels [1], and so far only one of them, the nicotinic acetylcholine receptor (nAChR, see Nicotinic Receptors), has been characterized in depth [2, 3]. The nAChR is a ligand-gated channel (see below) that does not select well among cations the channel is even permeable to choline, glycine ethylester and tris buffer cations. A number of other plasma... 

Non-selective Cation Channels. Figure 1 The nicotinic acetylcholine receptor (nAChR) is localized within the cell membrane above the cell membrane is the synaptic cleft, below the cytoplasm. Drawing of the closed (left) and open (right) nAChR showing acetylcholine (ACh) binding and cation movement. Dimensions of the receptor were taken from references [2, 3]. 

Miyazawa A, Fujiyoshi Y, Stowell M et al (1999) Nicotinic acetylcholine receptor at 4.6 A resolution transverse tunnels in the channel wall. J Mol Biol 288 765-786... 

The AMPA receptors for glutamate, the nicotinic acetylcholine receptor and the 5-HT3-receptor for serotonin are cation channels (Table 1). When they open, the major consequence is a sudden entry of Na+, depolarization and an excitatory postsynaptic potential (EPSP Fig. 1). 

Nicotinic Acetylcholine Receptor Nicotinic Receptors Nigrostriatal Tract/Pathway Nitrates... 

Bale AS, Smothers CT, Woodward JJ Inhibition of neuronal nicotinic acetylcholine receptors by the abused solvent, toluene. Br J Pharmacol 137 375-383, 2002... 

Nicotinic Acetylcholine Receptor Function Studied with Synthetic (+)-Anatoxin-a and Derivatives... 

Anatoxin-a is the most potent and most stereospecific nicotinic acetylcholine receptor agonist thus far identified. It is also highly selective for nicotinic receptors over muscarinic receptors. The molecular parameters which influence the binding affinity, channel activation, channel blockade, and receptor desensitization are being studied. Modifications of the carbonyl and amine moieties can reduce or nearly eliminate the receptor agonist potency of the compounds and also determine the channel blocking characteristics. 

These include nicotinic acetylcholine receptors, neuronal calcium channels, muscle sodium channels, vasopressin receptors, and iV-methyl-D-aspartate (NMDA) receptors. Some general features of the structure, function, and evolution of biologically active peptides isolated from Conus venom are presented. 

Peptides in the a-conotoxin family are inhibitors of nicotinic acetylcholine receptors. They were first isolated from C. geographus venom as components which cause paralysis in mice and fish when injected intraperitoneally (27). Early physiological experiments (28) indicated that a-conotoxins GI, GII, and GIA (see Table III) all act at the muscle end plate region. Mini end-plate potentials and end plate potentials evoked in response to nerve stimulation are inhibited in the presence of a-conotoxins in the nM to pM range. a-Conotoxin GI was subsequently shown to compete with rf-tubocurarine and a-bungarotoxin for the acetylcholine receptor (29). 

Lukas, RJ, Changeux, JP, Le Novere, N, Albuquerque, EX, Balfour, DJ, Berg, DK, Bertrand, D, Chiappinelli, VA, Clarke, PB, Collins, AC, Dani, JA, Grady, SR, Kellar, KJ, Lindstrom, JM, Marks, MJ, Quik, M, Taylor, PW and Wonnacott, S (1999) International Union of Pharmacology. XX. Current status of the nomenclature for nicotinic acetylcholine receptors and their subunits. Pharmacol. Rev. 51(2) 397 01. 

Unwin, N (1995) Acetylcholine receptor channel imaged in the open state. Nature 373 37-43. Unwin, N (2000) Nicotinic acetylcholine receptor and the structural basis of fast synaptic transmission. Phil. Trans. Roy. Soc. Lond. Ser. B 355 1813-1829. 

Changeux, JP (1990) The nicotinic acetylcholine receptor an allosteric protein protot5q)e of ligand-gated ion channels. Trends Pharmacol. Sci. 11 485M92. 

Lindstrom, JM (1997) Nicotinic acetylcholine receptors in health and disease. Mol. Neurohiol. 15 193-222. 

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