Journal
JOURNAL OF NEUROCHEMISTRY
Volume 77, Issue 3, Pages 957-960Publisher
BLACKWELL SCIENCE LTD
DOI: 10.1046/j.1471-4159.2001.00333.x
Keywords
anandamide; 2-arachidonoyl glycerol; c-Jun N-terminal kinase; lysophosphatidic acid
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Cannabinoid receptors (CBI-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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