The G-protein-coupled central cannabinoid receptor (CB1) has been shown to be functionally associated with several biological responses including inhibition of adenylate cyclase, modulation of ion channels and induction of the immediate-early gene Krox-24. Using stably transfected Chinese Hamster Ovary cells expressing human CB1 we show here that cannabinoid treatment induces both phosphorylation and activation of mitogen-activated protein (MAP) kinases, and that these effects are inhibited by SR 141716A, a selective CB1 antagonist. The two p42 and p44 kDa MAP kinases are activated in a time- and dose-dependent manner. The rank order of potency for the activation of MAP kinases with various cannabinoid agonists is CP-55940 > delta 9-tetrahydrocannabinol > WIN 55212.2, in agreement with the pharmacological profile of CB1. The activation of MAP kinases is blocked by pertussis toxin but not by treatment with hydrolysis-resistant cyclic AMP analogues. This suggests that the signal transduction pathway between CB1 and MAP kinases involves a pertussis-toxin-sensitive GTP-binding protein and is independent of cyclic AMP metabolism. This coupling of CB1 subtype and mitogenic signal pathway, also observed in the human astrocytoma cell line U373 MG, may explain the mechanism of action underlying cannabinoid-induced Krox-24 induction.
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December 1995
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Research Article|
December 01 1995
Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1 Available to Purchase
M Bouaboula;
M Bouaboula
*Sanofi Recherche, Department of Immunopharmacology, 371 rue du Professeur Joseph Blayac, 34184 Montpellier
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C Poinot-Chazel;
C Poinot-Chazel
*Sanofi Recherche, Department of Immunopharmacology, 371 rue du Professeur Joseph Blayac, 34184 Montpellier
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B Bourrié;
B Bourrié
*Sanofi Recherche, Department of Immunopharmacology, 371 rue du Professeur Joseph Blayac, 34184 Montpellier
‡Sanofi Recherche, 32-34 rue Marbeuf, 75008 Paris, France
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X Canat;
X Canat
*Sanofi Recherche, Department of Immunopharmacology, 371 rue du Professeur Joseph Blayac, 34184 Montpellier
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B Calandra;
B Calandra
†Sanofi Recherche, Voie n° 1, BP 137, 31676 Labège cedex
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M Rinaldi-Carmona;
M Rinaldi-Carmona
*Sanofi Recherche, Department of Immunopharmacology, 371 rue du Professeur Joseph Blayac, 34184 Montpellier
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G Le Fur;
G Le Fur
‡Sanofi Recherche, 32-34 rue Marbeuf, 75008 Paris, France
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P Casellas
P Casellas
*Sanofi Recherche, Department of Immunopharmacology, 371 rue du Professeur Joseph Blayac, 34184 Montpellier
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1995 The Biochemical Society, London
1995
Biochem J (1995) 312 (2): 637–641.
Citation
M Bouaboula, C Poinot-Chazel, B Bourrié, X Canat, B Calandra, M Rinaldi-Carmona, G Le Fur, P Casellas; Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1. Biochem J 1 December 1995; 312 (2): 637–641. doi: https://doi.org/10.1042/bj3120637
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