Elsevier

Life Sciences

Volume 56, Issues 23–24, 5 May 1995, Pages 2049-2056
Life Sciences

Cannabinod receptor and their ligand
Evaluation of cAMP involvement in cannabinoid-induced antinociception

https://doi.org/10.1016/0024-3205(95)00188-CGet rights and content

Abstract

It has been proposed that cannabinoids act at a Gi protein-coupled receptor to produce antinociception. One action of Gi-proteins is to decrease intracellular cAMP via inhibition of adenylyl cyclase activity. Although cannabinoid inhibition of forskolin-stimulated adenylyl cyclase is used as a confirmation of functional cannabinoid receptors, it is unknown whether this second messenger system specifically mediates cannabinoid-induced antinociception. This in vivo study was conducted using enantiomeric cAMP analogs, Rp-cAMPS (an antagonist) and Sp-cAMPS (an agonist), and the cAMP agonist Cl-cAMP to test the hypothesis that cannabinoid-induced antinociception is due to decreased adenylyl cyclase activity. None of the cAMP analogs, forskolin, or 1,9-dideoxy-forskolin affected Δ9-THC or CP-55,940-induced antinociception produced by intrathecal (i.t.) or intracerebroventricular (i.c.v.) injections in mice. Experiments were also conducted to investigate whether i.c.v. administration of Sp-cAMPS would block i.c.v. cannabinoid-induced antinociception in rats. Sp-cAMPS failed to block CP-55, 940-induced antinociception. However, Sp-cAMPS produced hyper-excitability and reactive behavior indicating that it did elicit a pharmacological effect. Although, adenylyl cyclase may mediate other cannabinoid-induced actions, these results do not support the hypothesis that it is involved in cannabinoid-induced antinociception. Alternatively, other effector systems such as calcium or potassium channels coupled to cannabinoid receptors may mediate cannabinoid-induced antinociception.

References (29)

  • P.B. Smith et al.

    Brain Res.

    (1992)
  • T. Braumann et al.

    Biochimica et Biophysica Acta

    (1986)
  • B.J. Connolly et al.

    Biochemical Pharmacology

    (1992)
  • P.A. Connelly et al.

    J. Biol. Chem.

    (1987)
  • P.J.M. Van Haastert et al.

    J. Bio. Chem.

    (1984)
  • A. Laurenza et al.

    TIPS

    (1989)
  • W.J. Martin et al.

    Brain Res.

    (1993)
  • W.L. Dewey

    Pharmacol. Rev.

    (1986)
  • B.R. Martin
  • A.H. Lichtman et al.

    I Pharmacol. Exp. Ther.

    (1991)
  • D.R. Compton et al.

    J. Pharmacol. Exp. Ther.

    (1993)
  • M.A. Brown et al.

    Ann. Rev. Physiol.

    (1990)
  • K. Mackie et al.
  • M.P. Caulfield et al.

    Br. J. Pharmacol.

    (1992)
  • Cited by (13)

    • Cannabis and endogenous cannabinoid systems

      1998, Drug and Alcohol Dependence
    View all citing articles on Scopus
    View full text