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Volume 375, Issue 1-2 p. 143-147
Research letter
Free Access

The peripheral cannabinoid receptor: adenylate cyclase inhibition and G protein coupling

Michael Bayewitch

Michael Bayewitch

Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel

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Tomer Avidor-Reiss

Tomer Avidor-Reiss

Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel

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Rivka Levy

Rivka Levy

Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel

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Jacob Barg

Jacob Barg

Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel

Therapuetic Community, Ramot Yehuda, Zoharim, Israel

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Raphael Mechoulam

Raphael Mechoulam

Department of Natural Products, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel

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Zvi Vogel

Zvi Vogel

Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel

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First published: November 13, 1995
Citations: 154
Corresponding author. Fax: (972) (8) 34-4131.

Abstract

Two cannabinoid receptors, designated neuronal (or CB1) and peripheral (or CB2), have recently been cloned. Activation of CB1 receptors leads to inhibition of adenylate cyclase and N-type voltage-dependent Ca2+ channels. Here we show, using a CB2 transfected Chinese hamster ovary cell line, that this receptor binds a variety of tricyclic cannabinoid ligands as well as the endogenous ligand anandamide. Activation of the CB2 receptor by various tricyclic cannabinoids inhibits adenylate cyclase activity and this inhibition is pertussis toxin sensitive indicating that this receptor is coupled to the Gi/G0 GTP-binding proteins. Interestingly, contrary to results with CB1, anandamide did not inhibit the CB2 coupled adenylate cyclase activity and δ 9-tetrahydrocannabinol had only marginal effects. These results characterize the CB2 receptor as a functional and distinctive member of the cannabinoid receptor family.