Actions of ethanolamine on cultured sensory neurones from neonatal rats
Some of the analgesic and antinociceptive properties of the endocannabinoid anandamide can be explained by modulation of voltage-activated ion channels. However, the products of anandamide metabolism by fatty acid amide hydroxylase may also contribute to the altered excitability of sensory neurones....
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Published in | Neuroscience letters Vol. 468; no. 3; pp. 326 - 329 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
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14.01.2010
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ISSN | 0304-3940 1872-7972 1872-7972 |
DOI | 10.1016/j.neulet.2009.11.025 |
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Abstract | Some of the analgesic and antinociceptive properties of the endocannabinoid anandamide can be explained by modulation of voltage-activated ion channels. However, the products of anandamide metabolism by fatty acid amide hydroxylase may also contribute to the altered excitability of sensory neurones. Ethanolamine is a product of metabolism of acylethanolamines including anandamide. In this study whole cell patch clamp recording and fura-2 Ca
2+ imaging techniques were used to characterize its actions on neonatal rat cultured dorsal root ganglion neurones. Ethanolamine (1
μM) increased the mean Ca
2+ transient produced by 1
mM caffeine and modulated Ca
2+ transients evoked by 60
mM KCl. Thapsigargicin (500
nM) inhibited the ethanolamine-evoked enhancement of Ca
2+ transients evoked by depolarisation. Voltage-activated K
+ currents were evoked from a holding potential of −70
mV by voltage step commands to 0
mV. Acute application of 1
μM ethanolamine produced irreversible current modulation. However, application of 100
nM ethanolamine reversibly increased or decreased K
+ currents. These effects of ethanolamine on voltage-activated K
+ currents were not sensitive to continual application of thapsigargicin. When applied alone thapsigargicin (500
nM) had no action on the mean K
+ current. In conclusion, ethanolamine may play distinct roles in the modulation of sensory neurone excitability by acting via different mechanisms to modulate K
+ channels and a component of intracellular Ca
2+ signalling. These data suggest that in a therapeutic context it may be difficult to predict the consequences of manipulating anandamide levels. |
---|---|
AbstractList | Some of the analgesic and antinociceptive properties of the endocannabinoid anandamide can be explained by modulation of voltage-activated ion channels. However, the products of anandamide metabolism by fatty acid amide hydroxylase may also contribute to the altered excitability of sensory neurones. Ethanolamine is a product of metabolism of acylethanolamines including anandamide. In this study whole cell patch clamp recording and fura-2 Ca(2+) imaging techniques were used to characterize its actions on neonatal rat cultured dorsal root ganglion neurones. Ethanolamine (1muM) increased the mean Ca(2+) transient produced by 1mM caffeine and modulated Ca(2+) transients evoked by 60mM KCl. Thapsigargicin (500nM) inhibited the ethanolamine-evoked enhancement of Ca(2+) transients evoked by depolarisation. Voltage-activated K(+) currents were evoked from a holding potential of -70mV by voltage step commands to 0mV. Acute application of 1muM ethanolamine produced irreversible current modulation. However, application of 100nM ethanolamine reversibly increased or decreased K(+) currents. These effects of ethanolamine on voltage-activated K(+) currents were not sensitive to continual application of thapsigargicin. When applied alone thapsigargicin (500nM) had no action on the mean K(+) current. In conclusion, ethanolamine may play distinct roles in the modulation of sensory neurone excitability by acting via different mechanisms to modulate K(+) channels and a component of intracellular Ca(2+) signalling. These data suggest that in a therapeutic context it may be difficult to predict the consequences of manipulating anandamide levels.Some of the analgesic and antinociceptive properties of the endocannabinoid anandamide can be explained by modulation of voltage-activated ion channels. However, the products of anandamide metabolism by fatty acid amide hydroxylase may also contribute to the altered excitability of sensory neurones. Ethanolamine is a product of metabolism of acylethanolamines including anandamide. In this study whole cell patch clamp recording and fura-2 Ca(2+) imaging techniques were used to characterize its actions on neonatal rat cultured dorsal root ganglion neurones. Ethanolamine (1muM) increased the mean Ca(2+) transient produced by 1mM caffeine and modulated Ca(2+) transients evoked by 60mM KCl. Thapsigargicin (500nM) inhibited the ethanolamine-evoked enhancement of Ca(2+) transients evoked by depolarisation. Voltage-activated K(+) currents were evoked from a holding potential of -70mV by voltage step commands to 0mV. Acute application of 1muM ethanolamine produced irreversible current modulation. However, application of 100nM ethanolamine reversibly increased or decreased K(+) currents. These effects of ethanolamine on voltage-activated K(+) currents were not sensitive to continual application of thapsigargicin. When applied alone thapsigargicin (500nM) had no action on the mean K(+) current. In conclusion, ethanolamine may play distinct roles in the modulation of sensory neurone excitability by acting via different mechanisms to modulate K(+) channels and a component of intracellular Ca(2+) signalling. These data suggest that in a therapeutic context it may be difficult to predict the consequences of manipulating anandamide levels. Some of the analgesic and antinociceptive properties of the endocannabinoid anandamide can be explained by modulation of voltage-activated ion channels. However, the products of anandamide metabolism by fatty acid amide hydroxylase may also contribute to the altered excitability of sensory neurones. Ethanolamine is a product of metabolism of acylethanolamines including anandamide. In this study whole cell patch clamp recording and fura-2 Ca 2+ imaging techniques were used to characterize its actions on neonatal rat cultured dorsal root ganglion neurones. Ethanolamine (1 μM) increased the mean Ca 2+ transient produced by 1 mM caffeine and modulated Ca 2+ transients evoked by 60 mM KCl. Thapsigargicin (500 nM) inhibited the ethanolamine-evoked enhancement of Ca 2+ transients evoked by depolarisation. Voltage-activated K + currents were evoked from a holding potential of −70 mV by voltage step commands to 0 mV. Acute application of 1 μM ethanolamine produced irreversible current modulation. However, application of 100 nM ethanolamine reversibly increased or decreased K + currents. These effects of ethanolamine on voltage-activated K + currents were not sensitive to continual application of thapsigargicin. When applied alone thapsigargicin (500 nM) had no action on the mean K + current. In conclusion, ethanolamine may play distinct roles in the modulation of sensory neurone excitability by acting via different mechanisms to modulate K + channels and a component of intracellular Ca 2+ signalling. These data suggest that in a therapeutic context it may be difficult to predict the consequences of manipulating anandamide levels. Some of the analgesic and antinociceptive properties of the endocannabinoid anandamide can be explained by modulation of voltage-activated ion channels. However, the products of anandamide metabolism by fatty acid amide hydroxylase may also contribute to the altered excitability of sensory neurones. Ethanolamine is a product of metabolism of acylethanolamines including anandamide. In this study whole cell patch clamp recording and fura-2 Ca(2+) imaging techniques were used to characterize its actions on neonatal rat cultured dorsal root ganglion neurones. Ethanolamine (1muM) increased the mean Ca(2+) transient produced by 1mM caffeine and modulated Ca(2+) transients evoked by 60mM KCl. Thapsigargicin (500nM) inhibited the ethanolamine-evoked enhancement of Ca(2+) transients evoked by depolarisation. Voltage-activated K(+) currents were evoked from a holding potential of -70mV by voltage step commands to 0mV. Acute application of 1muM ethanolamine produced irreversible current modulation. However, application of 100nM ethanolamine reversibly increased or decreased K(+) currents. These effects of ethanolamine on voltage-activated K(+) currents were not sensitive to continual application of thapsigargicin. When applied alone thapsigargicin (500nM) had no action on the mean K(+) current. In conclusion, ethanolamine may play distinct roles in the modulation of sensory neurone excitability by acting via different mechanisms to modulate K(+) channels and a component of intracellular Ca(2+) signalling. These data suggest that in a therapeutic context it may be difficult to predict the consequences of manipulating anandamide levels. Some of the analgesic and antinociceptive properties of the endocannabinoid anandamide can be explained by modulation of voltage-activated ion channels. However, the products of anandamide metabolism by fatty acid amide hydroxylase may also contribute to the altered excitability of sensory neurones. Ethanolamine is a product of metabolism of acylethanolamines including anandamide. In this study whole cell patch clamp recording and fura-2 Ca super(2+) imaging techniques were used to characterize its actions on neonatal rat cultured dorsal root ganglion neurones. Ethanolamine (1 kM) increased the mean Ca super(2+) transient produced by 1 mM caffeine and modulated Ca super(2+) transients evoked by 60 mM KCl. Thapsigargicin (500 nM) inhibited the ethanolamine-evoked enhancement of Ca super(2+) transients evoked by depolarisation. Voltage-activated K super(+) currents were evoked from a holding potential of -70 mV by voltage step commands to 0 mV. Acute application of 1 kM ethanolamine produced irreversible current modulation. However, application of 100 nM ethanolamine reversibly increased or decreased K super(+) currents. These effects of ethanolamine on voltage-activated K super(+) currents were not sensitive to continual application of thapsigargicin. When applied alone thapsigargicin (500 nM) had no action on the mean K super(+) current. In conclusion, ethanolamine may play distinct roles in the modulation of sensory neurone excitability by acting via different mechanisms to modulate K super(+) channels and a component of intracellular Ca super(2+) signalling. These data suggest that in a therapeutic context it may be difficult to predict the consequences of manipulating anandamide levels. |
Author | Adjei, Gloria Allen-Redpath, Keith Scott, Roderick H. Khairy, Hesham |
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Cites_doi | 10.1523/JNEUROSCI.4071-08.2009 10.1038/nrd2553 10.1111/j.1469-7793.2000.t01-1-00247.x 10.1186/1744-8069-5-35 10.1016/j.pharmthera.2005.09.009 10.1186/1471-2210-6-10 10.1054/plef.2001.0362 10.1038/sj.bjp.0705723 10.1038/bjp.2008.93 10.1016/S1471-4892(01)00120-5 10.1038/sj.bjp.0707456 10.1016/S0028-3908(00)00135-0 10.1038/sj.emboj.7600784 10.1046/j.1471-4159.2003.01550.x |
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Keywords | Intracellular calcium stores Voltage-activated potassium currents Dorsal root ganglion Endocannabinoids Thapsigargicin Spinal cord Calcium Rat Rodentia Central nervous system Ionic current Cannabinoid Vertebrata Mammalia Endocannabinoid Animal Spinal ganglion Intracellular Potassium |
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SubjectTerms | Animals Animals, Newborn Biological and medical sciences Calcium Signaling Cells, Cultured Dorsal root ganglion Endocannabinoids Ethanolamine - metabolism Ethanolamine - pharmacology Fundamental and applied biological sciences. Psychology Ganglia, Spinal - cytology Intracellular calcium stores Patch-Clamp Techniques Potassium Channels, Voltage-Gated - physiology Potassium Chloride - pharmacology Rats Sensory Receptor Cells - drug effects Sensory Receptor Cells - physiology Thapsigargicin Vertebrates: nervous system and sense organs Voltage-activated potassium currents |
Title | Actions of ethanolamine on cultured sensory neurones from neonatal rats |
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