Carbon monoxide is a rapid modulator of recombinant and native P2X(2) ligand-gated ion channels

Wilkinson, William James, Gadeberg, H.C., Harrison, A. W. J., Allen, Nicholas Denby ORCID: https://orcid.org/0000-0003-4009-186X, Riccardi, Daniela ORCID: https://orcid.org/0000-0002-7322-3163 and Kemp, Paul J ORCID: https://orcid.org/0000-0003-2773-973X 2009. Carbon monoxide is a rapid modulator of recombinant and native P2X(2) ligand-gated ion channels. British Journal of Pharmacology 158 (3) , pp. 862-871. 10.1111/j.1476-5381.2009.00354.x

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Abstract

Background and purpose:  Carbon monoxide (CO) is a potent modulator of a wide variety of physiological processes, including sensory signal transduction. Many afferent sensory pathways are dependent upon purinergic neurotransmission, but direct modulation of the P2X purinoceptors by this important, endogenously produced gas has never been investigated. Experimental approach:  Whole-cell patch-clamp experiments were used to measure ATP-elicited currents in human embryonic kidney 293 cells heterologously expressing P2X2, P2X3, P2X2/3 and P2X4 receptors and in rat pheochromocytoma (PC12) cells known to express native P2X2 receptors. Modulation was investigated using solutions containing CO gas and the CO donor molecule, tricarbonyldichlororuthenium (II) dimer (CORM-2). Key results:  CO was a potent and selective modulator of native P2X2 receptors, and these effects were mimicked by a CO donor (CORM-2). Neither pre-incubation with 8-bromoguanosine-3′,5′-cyclomonophosphate nor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (a potent blocker of soluble guanylyl cyclase) affected the ability of the CO donor to enhance the ATP-evoked P2X2 currents. The CO donor caused a small, but significant inhibition of currents evoked by P2X2/3 and P2X4 receptors, but was without effect on P2X3 receptors. Conclusions and implications:  These data provided an explanation for how CO might regulate sensory neuronal traffic in physiological reflexes such as systemic oxygen sensing but also showed that CO could be used as a selective pharmacological tool to assess the involvement of homomeric P2X2 receptors in physiological systems.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Neuroscience and Mental Health Research Institute (NMHRI)
Publisher:	Wiley-Blackwell
ISSN:	0007-1188
Last Modified:	17 Oct 2022 10:37
URI:	https://orca.cardiff.ac.uk/id/eprint/8791

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