Receptors For nicotine

Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, Offermanns S (2003) PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med 9 352-355... 

A. Lorenzen, C. Stannek, H. Lang, V. Andrianov, I. Kalvinsii, and L). ScHWABE, Characterization of a G protein-coupled receptor for nicotinic acid. Mol. Pharmacol., 2001, 59, 349-357. 

Tobacco is another commonly abused stimulant. It contains nicotine as the major stimulant. As mentioned earlier (Sect. 17.1), our brain has a receptor for nicotine, a part of acetylcholine receptor. Nicotine is an alkaloid and its structure is shown in Fig. 17.2. Tobacco plants produce nicotine as a defense chemical, to kill some insects. Nicotine has indeed been used as an insecticide for long. It is poisonous to human body, too, and a small amount can kill. In smaller quantities (as found in inhaled smoke), it can act as a stimulant interacting with the receptor as mentioned earlier, and it is quite addictive. 

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). 

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. 

The debut of the selective AChR agonist (+)-anatoxin-a has provided a new tool for AChR physiology and pharmacology. (+)-Anatoxin not only has high affinity for the nicotinic AChR but it also has high selectivity for nicotinic over muscarinic receptors in the mammalian CNS. Recently, the use of (+)-anatoxin-a was essential to the identification of nicotinic receptors on cultured neurons (4), We are studying the features which allow it to bind with high affinity to the peripheral and central nicotinic receptors and the kinetic effects on receptor conformational... 

Another possible target for toxins are the receptors for neurotransmitters since such receptors are vital, especially for locomotion. In vertebrates the most strategic receptor is that for acetylcholine, the nicotinic receptor. In view of the breadth of action of the various conotoxins it is perhaps not surprising that alpha-conotoxin binds selectively to the nicotinic receptor. It is entirely possible that similar blockers exist for the receptors which are vital to locomotion in lower species. As mentioned previously, lophotoxin effects vertebrate neuromuscular junctions. It appears to act on the end plate region of skeletal muscle (79,59), to block the nicotinic receptor at a site different from the binding sites for other blockers (81). 

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. 

There is some evidence that receptors for other neurotransmitters on 5-HT nerve terminals also modify release of 5-HT. These include nicotinic receptors (increase release from striatal synaptosomes), a2A-adrenoceptors (depress cortical release) and H3-receptors (cortical depression). Because changes in 5-HT release on activation of these receptors is evident in synaptosomal preparations, it is likely that these are true heteroceptors . 

The nAChR subtypes vary in response to pharmacological manipulation. The a7 receptors have a low affinity for nicotine and are sensitive to a-bungarotoxin (a-BTX) antagonism, whereas the heteromeric nAChRs are not.14 The p2 containing (p2 asterisk denotes the presence of additional subunits) nAChRs have the highest affinity for nicotine binding and some selectivity for antagonism... 

Mitsis, E.M., van Dyck, C.H., Krantzler, E. et al. Prolonged occupancy of nicotinic acetylcholine receptors by nicotine in human brain a preliminary study. Paper presented at the Annual Meeting of the Society for Research on Nicotine and Tobacco, Orlando, FL, 2006. 

Paterson, N.E., Markou, A. The metabotropic glutamate receptor 5 antagonist MPEP decreased break points for nicotine, cocaine and food in rats. Psychopharmacology (Berlin). 179 255, 2005. 

Nomikos, G.G., Schilstrom, B., Hilderbrand, B.E., Panagis, G., Grenhoff, J., Svensson, T.H. Role of alpha7 nicotinic receptors in nicotine dependence and implications for psychiatric illness. Behav. Brain Res. 113 97, 2000. 

Cholinergic receptors Receptors for acetylcholine are classified into muscarinic (muscarine is a selective agonist) and nicotinic (nicotine is a selective agonist). There are five muscarinic (mj to m5) and two nicotinic (neuronal, or ganglionic, and skeletal muscular) subtypes. 

In this scheme, M <1 and K equilibrium constants. Direct binding experiments have confirmed the generality of this scheme for nicotinic receptors. Thus, distinct conformational states govern the different temporal responses that ensue upon addition of a ligand to the nicotinic receptor. No direct energy input or covalent modification of the receptor channel is required. 

Nicotine is an agonist at the nicotinic acetylcholine receptor (nAChR) 921 The ventral tegmental area (VTA) is a critical site for nicotine action 921... 

In smooth muscle, just as in other cells, extracellular stimuli typically evoke an increase in cytosolic Ca2+ concentration ([Ca2+]c) by stimulating release of Ca2+ from intracellular stores or Ca2+ entry across the plasma membrane. Members of two closely related families of intracellular Ca2+ channels, ryanodine receptors and the receptors for inositol-1,4,5-trisphosphate (InsP3) appear to be expressed in all smooth muscle cells and they provide the most important route for release of Ca2+ from the sarcoplasmic reticulum (Sutko Airey 1996). The roles of additional Ca2+-mobilizing messengers, such as nicotinic acid adenine dinucleotide... 

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