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. 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.
Khairy
Hesham
H
Institute of Medical Sciences, School of Medical Science, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
Adjei
Gloria
G
Allen-Redpath
Keith
K
Scott
Roderick H
RH
D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling; D002478:Cells, Cultured; D019856:Ethanolamine / Q000378:metabolism* / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*
D024642:Potassium Channels, Voltage-Gated; D019856:Ethanolamine; D011189:Potassium Chloride