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Carbon monoxide is a rapid modulator of recombinant and native P2X(2) ligand-gated ion channels.
- Source :
- British Journal of Pharmacology; Oct2009, Vol. 158 Issue 3, p862-871, 10p
- Publication Year :
- 2009
-
Abstract
- <bold>Background and Purpose: </bold>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.<bold>Experimental Approach: </bold>Whole-cell patch-clamp experiments were used to measure ATP-elicited currents in human embryonic kidney 293 cells heterologously expressing P2X(2), P2X(3), P2X(2/3) and P2X(4) receptors and in rat pheochromocytoma (PC12) cells known to express native P2X(2) receptors. Modulation was investigated using solutions containing CO gas and the CO donor molecule, tricarbonyldichlororuthenium (II) dimer (CORM-2).<bold>Key Results: </bold>CO was a potent and selective modulator of native P2X(2) 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 P2X(2) currents. The CO donor caused a small, but significant inhibition of currents evoked by P2X(2/3) and P2X(4) receptors, but was without effect on P2X(3) receptors.<bold>Conclusions and Implications: </bold>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 P2X(2) receptors in physiological systems. [ABSTRACT FROM AUTHOR]
- Subjects :
- PHEOCHROMOCYTOMA
CARBON monoxide
ION channels
CELLULAR signal transduction
NEURAL transmission
GENE expression
LABORATORY rats
ANIMAL experimentation
BIOCHEMISTRY
CELL lines
CELL receptors
COMPARATIVE studies
CYTOLOGICAL techniques
DRUGS
LIGANDS (Biochemistry)
PHENOMENOLOGY
RESEARCH methodology
MEDICAL cooperation
NEUROTRANSMITTERS
RATS
RECOMBINANT proteins
RESEARCH
RESEARCH funding
EVALUATION research
CHEMICAL inhibitors
CELL physiology
Subjects
Details
- Language :
- English
- ISSN :
- 00071188
- Volume :
- 158
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- British Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 65012714
- Full Text :
- https://doi.org/10.1111/j.1476-5381.2009.00354.x