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 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). KEY RESULTS: 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. 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 P2X(2) receptors in physiological systems.
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 humanembryonic kidney 293 cells heterologously expressing P2X(2), P2X(3), P2X(2/3) and P2X(4) receptors and in ratpheochromocytoma (PC12) cells known to express native P2X(2) receptors. Modulation was investigated using solutions containing CO gas and the COdonor molecule, tricarbonyldichlororuthenium (II) dimer (CORM-2). KEY RESULTS:CO was a potent and selective modulator of native P2X(2) receptors, and these effects were mimicked by a COdonor (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 COdonor to enhance the ATP-evoked P2X(2) currents. The COdonor 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. 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 P2X(2) receptors in physiological systems.
Authors: Roberto Motterlini; James E Clark; Roberta Foresti; Padmini Sarathchandra; Brian E Mann; Colin J Green Journal: Circ Res Date: 2002-02-08 Impact factor: 17.367
Authors: Jonathan H Jaggar; Charles W Leffler; Serguei Y Cheranov; Dilyara Tcheranova; Shuyu E; Xiaoyang Cheng Journal: Circ Res Date: 2002-10-04 Impact factor: 17.367
Authors: Samuel J Fountain; Katie Parkinson; Mark T Young; Lishuang Cao; Christopher R L Thompson; R Alan North Journal: Nature Date: 2007-07-12 Impact factor: 49.962
Authors: Andrés Jara-Oseguera; Itzel G Ishida; Gisela E Rangel-Yescas; Noel Espinosa-Jalapa; José A Pérez-Guzmán; David Elías-Viñas; Ronan Le Lagadec; Tamara Rosenbaum; León D Islas Journal: J Biol Chem Date: 2011-03-17 Impact factor: 5.157