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Functional lipidomics. Calcium-independent activation of endocannabinoid/endovanilloid lipid signalling in sensory neurons by protein kinases C and A and thrombin.
- Source :
-
Neuropharmacology [Neuropharmacology] 2008 Dec; Vol. 55 (8), pp. 1274-9. Date of Electronic Publication: 2008 Feb 06. - Publication Year :
- 2008
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Abstract
- N-arachidonoylethanolamine (anandamide, AEA), is a full agonist at both cannabinoid CB(1) receptors and "transient receptor potential vanilloid" type 1 (TRPV1) channels, and N-palmitoylethanolamine (PEA) potentiates these effects. In neurons of the rat dorsal root ganglia (DRG), TRPV1 is activated and/or sensitised by AEA as well as upon activation of protein kinases C (PKC) and A (PKA). We investigated here the effect on AEA levels of PKC and PKA activators in DRG neurons. AEA levels were significantly enhanced by both phorbol-miristoyl-acetate (PMA), a typical PKC activator, and forskolin (FSK), an adenylate cyclase stimulant, as well as by thrombin, which also activates PKC by stimulating protease-activated receptors (PARs). The levels of the other endocannabinoid and TRPV1-inactive compound, 2-arachidonoylglycerol (2-AG), were enhanced only by thrombin and to a lesser extent than AEA, whereas PEA was not affected by any of the treatments. Importantly, FSK- and PMA-induced elevation of AEA levels was not sensitive to intracellular Ca2+ chelation with BAPTA-acetoxymethyl (AM) ester. In human embryonic kidney (HEK-293) cells, which constitutively express PARs, thrombin, PMA and FSK elevated AEA levels, and the effects of the two former compounds were counteracted by the PKC inhibitor, RO318220, whereas the effect of FSK was reduced by the PKA inhibitor RpcAMPs. In conclusion, we report that AEA levels are stimulated by both PKC, either directly or after thrombin receptor activation, and PKA, possibly in a way independent from intracellular calcium. Since AEA activates TRPV1, these findings may suggest the existence of an amplificatory cascades on this receptor in sensory neurons.
- Subjects :
- Animals
Animals, Newborn
Arachidonic Acids metabolism
Cannabinoid Receptor Modulators
Cells, Cultured
Colforsin pharmacology
Egtazic Acid analogs & derivatives
Egtazic Acid pharmacology
Endocannabinoids
Ganglia, Spinal cytology
Glycerides metabolism
Humans
Rats
Rats, Sprague-Dawley
Receptors, Proteinase-Activated metabolism
Signal Transduction drug effects
Tetradecanoylphorbol Acetate pharmacology
Calcium metabolism
Cyclic AMP-Dependent Protein Kinases metabolism
Protein Kinase C metabolism
Sensory Receptor Cells drug effects
Thrombin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0028-3908
- Volume :
- 55
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 18329052
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2008.01.010