Cannabinoids activate p38 mitogen-activated protein kinases through CB1 receptors in hippocampus.
Cannabinoid receptors (CB1-R) are the target of a novel class of neuromodulators, the endocannabinoids. Yet, their signalling mechanisms in adult brain are poorly understood. We report that, in rat and mouse hippocampal slices, anandamide and 2-arachidonoylglycerol, synthetic cannabinoids, and delta(9)-tetrahydrocannabinol activated p38 mitogen-activated protein kinases (MAPK), but not c-Jun N-terminal kinase (JNK). In contrast, lysophosphatidic acid (LPA), a lipid messenger acting on different receptors, increased both p38-MAPK and JNK phosphorylation. The effects of cannabinoids on p38-MAPK were mediated through activation of CB1-R because they were blocked in the presence of SR 141716 A and absent in CB1-R knockout mice, two conditions that did not alter the effects of LPA. The activation of p38-MAPK by cannabinoids was insensitive to inhibitors of SRC: These results provide new insights into the cellular mechanisms by which cannabinoids exert their effects in hippocampus.
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INSERM U536, Institut du Fer à Moulin, Paris, France.
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Parmentier
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Girault
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D000818:Animals; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000201:enzymology*; D048031:JNK Mitogen-Activated Protein Kinases; D008246:Lysophospholipids / Q000494:pharmacology; D048670:MAP Kinase Kinase 4; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D008246:Lysophospholipids; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases