Heavy metals modulate the activity of the purinergic P2X<sub>4</sub> receptor

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dc.contributor.authorCoddou, C
dc.contributor.authorLorca, RA
dc.contributor.authorAcuña-Castillo, C
dc.contributor.authorGrauso, M
dc.contributor.authorRassendren, F
dc.contributor.authorHuidobro-Toro, JP
dc.date.accessioned2025-01-21T01:07:13Z
dc.date.available2025-01-21T01:07:13Z
dc.date.issued2005
dc.description.abstractTo further characterize the nature of the regulatory metal-binding sites of the rat P2X(4) receptor, several transition heavy metals were tested to examine their ability to mimic the facilitator action of zinc or the inhibitory action of copper. cDNA coding for the rat P2X(4) receptor was injected into Xenopus laevis oocytes; the two-electrode voltage-clamp technique was used to measure and quantify the ATP-evoked currents in the absence or presence of the metals. Cadmium facilitated the ATP-gated currents in a reversible and voltage-independent manner; maximal potentiation occurred within less than 1 min.
dc.description.abstractCadmium displaced leftward, in a concentration-dependent manner, the ATP concentration-response curve. In contrast, mercury reduced the ATP-gated currents in a reversible, time, and concentration manner. Maximal inhibition occurred after about 5 min of metal application. Cobalt also augmented the ATP-evoked currents, but its action was long lasting and did not reverse even after 45 min of metal washout. Other metals such as lead, nickel, manganese, silver, or gallium did not significantly alter the ATP-gated currents. The co-application of cadmium plus zinc or mercury plus copper caused additive effects. Mutation of H140 by alanine (H140A) augmented both the cadmium-induced facilitation and the mercury-induced inhibition. In contrast, the H241A mutant showed characteristics indistinguishable from the wild type. The H286A mutant showed a normal cadmium-induced potentiation, but an increased mercury inhibition. Out of the metals examined, only cadmium mimicked closely the action of zinc, evidencing commonalities. While mercury mimicked the action of copper, both metals apparently interact at distinct metal-binding sites. The present findings allow us to infer that heavy metals modulate the P2X(4) receptor by acting in at least three separate metal-binding sites. (C) 2004 Elsevier Inc. All rights reserved.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.taap.2004.06.015
dc.identifier.eissn1096-0333
dc.identifier.issn0041-008X
dc.identifier.urihttps://doi.org/10.1016/j.taap.2004.06.015
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96294
dc.identifier.wosidWOS:000226331900001
dc.issue.numero2
dc.language.isoen
dc.pagina.final131
dc.pagina.inicio121
dc.revistaToxicology and applied pharmacology
dc.rightsacceso restringido
dc.subjectP2X(4) receptor
dc.subjectheavy metals
dc.subjectmetal-binding sites
dc.subjectmetal modulation
dc.subjectcadmium
dc.subjectmercury
dc.subjectcobalt
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleHeavy metals modulate the activity of the purinergic P2X<sub>4</sub> receptor
dc.typeartículo
dc.volumen202
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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