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Artículo

A novel pharmacological activity of caffeine in the cholinergic system

Fabiani, CamilaIcon ; Murray, Ana PaulaIcon ; Corradi, JeremiasIcon ; Antollini, Silvia SusanaIcon
Fecha de publicación: 06/2018
Editorial: Pergamon-Elsevier Science Ltd
Revista: Neuropharmacology
ISSN: 0028-3908
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Biofísica

Resumen

Cholinergic deficit is regarded as an important factor responsible for Alzheimer's disease (AD) symptoms. Acetylcholinesterase (AChE) and nicotinic receptor (AChR) are two molecular targets for the treatment of this disease. We found here that methanolic extracts of Camellia sinensis exhibited anticholinesterase activity and induced AChR conformational changes. From bioguided fractionation we confirmed that caffeine was the active compound exerting such effects. It is well-known that caffeine acts as an inhibitor of AChE and here we explored the effect of caffeine on the AChR by combining single channel recordings and fluorescent measurements. From single channel recordings we observed that caffeine activated both muscle and α7 AChRs at low concentrations, and behaved as an open channel blocker which was evident at high concentrations. Fluorescent measurements were performed with the conformational sensitive probe crystal violet (CrV) and AChR rich membranes from Torpedo californica. Caffeine induced changes in the K D value of CrV in a concentration-dependent manner taking the AChR closer to a desentisized state. In the presence of α-bungarotoxin, an AChR competitive antagonist, high concentrations of caffeine increased the K D value of CrV, compatible with a competition with CrV molecules for the luminal channel. Our electrophysiological and fluorescent experiments show that caffeine has a dual effect on nicotinic receptors, behaving as an agonist and an ion channel blocker, probably through distinct AChR sites with quite different affinities. Thus, caffeine or its derivatives can be considered for the design of promising multitarget-directed drugs for AD treatment by modulation of different targets in the cholinergic pathway.
Palabras clave: ACETYLCHOLINESTERASE , ALZHEIMER'S DISEASE , CAFFEINE , ELECTROPHYSIOLOGY , FLUORESCENCE SPECTROSCOPY , NICOTINIC RECEPTORS
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/87420
URL: https://www.sciencedirect.com/science/article/pii/S0028390818301539
DOI: https://doi.org/10.1016/j.neuropharm.2018.03.041
Colecciones
Articulos(INIBIBB)
Articulos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Articulos(INQUISUR)
Articulos de INST.DE QUIMICA DEL SUR
Citación
Fabiani, Camila; Murray, Ana Paula; Corradi, Jeremias; Antollini, Silvia Susana; A novel pharmacological activity of caffeine in the cholinergic system; Pergamon-Elsevier Science Ltd; Neuropharmacology; 135; 6-2018; 464-473
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