Nicotine is a volatile alkaloid that interacts with the ionotropic acetylcholine receptors, thus named nicotinic receptors

• Autores: Miguel Díaz Hernández, Francisco Javier Gualix Sánchez, Rosa Gómez Villafuertes, Enrique Castro, Jesús Pintor, María Teresa Miras Portugal
• Localización: Anales de la Real Academia Nacional de Farmacia, ISSN-e 1697-4298, ISSN 0034-0618, Nº. 4 2, 2000, pág. 1
• Idioma: inglés
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  • The nicotinic receptors are very abundant at the Torpedo electric organ cholinergic synapses, allowing their characterisation. These receptors are analogous to the mammalian neuromuscular junction, they are pentameric and contain five subunits, two ?, and one of each other (2?1?1??). The protein family of ? subunits contain 9 members, and that of ? subunits four members. Their combinations originate a large number of different receptors with specific distribution in the nervous system. Neural nicotinic receptors can be classified in two main groups, the first one are receptors inhibited by ?-bungarotoxin and containing exclusively the ?7 and ?8 subunits, originating homomeric receptors (5?7 or 5?8). The second group of neural nicotinic receptors is not sensitive to ?-bungarotoxin, but they are activated by epibatidine. They contain a larger variety of ? and ? subunits and the combination ?4/?2 is very frequent. Both neural nicotinic receptors when stimulated allow the Ca2+ and Na+ entrance, originating a membrane depolarisation and subsequently the exocytotic release of neurotransmitters. Nicotinic receptors are widely distributed in mammalian brain, and their localisation in nerve terminals is mainly presynaptic. There, they facilitate, potentiate or induce the neurotransmitter release of the acetylcholine itself, or other neurotransmitters, such as glutamate, noradrenaline or GABA. Special mention deserves the facilitation of dopamine release from striatum/nucleus accumbens that provide a plausible explanation on tobacco smoking addiction. This wide effect on secretion potentiation carried out by acetylcholine via nicotinic receptors could explain the fatal consequences derived from the cholinergic neurones lost, as it is the case in Alzheimer disease. The presence of nicotinic receptors in isolated nerve terminals was studied by microfluorescence coupled to video imaging, measuring the Ca2+ entrance with a fluorescent die, as it was also done for the ATP and ApnA ionotropic receptors. At the same terminals by immunohistochemical studies, the presence of the P2X3, subtype of ATP receptors was shown. ATP and Ap5A were able to induce the release of acetilcholine from rat midbrain synaptic terminals. These results corroborate the idea of a certainly complex cross-talk between nucleotide and nicotinic receptors at the same presynaptic terminals, with relevant consequences for neural functioning and future pharmacology.