Título

Physiological concentrations of zinc have dual effects on P2X myenteric receptors of guinea pig

Autor

Liliana Hortencia Méndez Barredo

JESSICA GABRIELA RODRIGUEZ MELENDEZ

KAREN SARAHI GOMEZ CORONADO

Raquel Guerrero Alba

Eduardo Emmanuel Valdez Morales

ROSA ESPINOSA LUNA

ALMA ROSA BARAJAS ESPINOSA

Carlos Barajas López

Nivel de Acceso

Acceso Abierto

Identificador alterno

doi: https://doi.org/10.1007/s10571-018-0612-7

Resumen o descripción

"We, hereby, characterize the pharmacological effects of physiological concentrations of Zinc on native myenteric P2X receptors from guinea-pig small intestine and on P2X2 isoforms present in most myenteric neurons. This is the first study describing opposite effects of Zinc on these P2X receptors. It was not possible to determine whether both effects were concentration dependent, yet the inhibitory effect was mediated by competitive antagonism and was concentration dependent. The potentiating effect appears to be mediated by allosteric changes induced by Zinc on P2X myenteric channels, which is more frequently observed in myenteric neurons with low zinc concentrations. In P2X2-1 and P2X2-2 variants, the inhibitory effect is more common than in P2X myenteric channels. However, in the variants, the potentiatory effect is of equal magnitude as the inhibitory effect. Inhibitory and potentiatory effects are likely mediated by different binding sites that appear to be present on both P2X2 variants. In conclusion, in myenteric native P2X receptors, Zinc has quantitatively different pharmacological effects compared to those observed on homomeric channels: P2X2-1 and P2X2-2. Potentiatory and inhibitory Zinc effects upon these receptors are mediated by two different binding sites. All our data suggest that myenteric P2X receptors have a more complex pharmacology than those of the recombinant P2X2 receptors, which is likely related to other subunits known to be expressed in myenteric neurons. Because these dual effects occur at Zinc physiological concentrations, we suggest that they could be involved in physiological and pathological processes."

Editor

Springer

Fecha de publicación

2018

Tipo de publicación

Artículo

Versión de la publicación

Versión enviada

Formato

application/pdf

Sugerencia de citación

Méndez-Barredo, L.H., Rodríguez-Meléndez, J.G., Gómez-Coronado, K.S. et al. Cell Mol Neurobiol (2018) 38: 1439. https://doi.org/10.1007/s10571-018-0612-7

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