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

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

  1. Anonymous
    Michael Bayewitch a, Tomer Avidor-Reiss a, Rivka Levy a, Jacob Barg a'b, Raphael Mechoulam c,
    Zvi Vogel a'*
    aDepartment of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, lsrael
    bTherapuetic Community, Ramot Yehuda, Zoharim, Israel
    CDepartment of Natural Products, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel

    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 Ca 2+ 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 tricydic cannabinoids inhibits adenylate cyclase activity
    and this inhibition is pertussis toxin sensitive indicating that
    this receptor is coupled to the GilGo GTP-binding proteins. Interestingly,
    contrary to results with CB1, anandamide did not inhibit
    the CB2 coupled adenylate cyclase activity and A9-tetrahydro -
    cannabinol had only marginal effects. These results characterize
    the CB2 receptor as a functional and distinctive member of the
    cannabinoid receptor family.