Effects of delta 9-tetrahydrocannabinol on glucagon receptor coupling to adenylate cyclase in rat liver plasma membranes

Biochem Pharmacol. 1986 Aug 15;35(16):2797-803. doi: 10.1016/0006-2952(86)90192-9.


Delta-Tetrahydrocannabinol (delta 9-THC), the principal psychoactive constituent of Cannabis sativa, was found to increase glucagon activation of liver plasma membrane adenylate cyclase. In the presence of 30 microM delta 9-THC, the EC50 for glucagon was decreased by 60% from 7.6nM to 3.1 nM. 11-OH-delta 9-THC, a psychoactive metabolite of delta 9-THC, also increased glucagon activation of adenylate cyclase while two cannabinoids without marihuana-like psychoactive potency, cannabinol and cannabidiol, did not. At 30 microM, delta 9-THC either slightly decreased or had no effect on the activation of adenylate cyclase by GTP, Gpp(NH)p, fluoride ion, forskolin or ATP alone. Delta 9-THC had no effect on the binding of [125I] glucagon to liver plasma membranes. Arrhenius plots demonstrated that delta 9-THC and 11-OH-delta 9-THC, but not CBD, decreased the activation energy above the break temperature. Therefore, delta 9-THC increased the coupling of the glucagon receptor to adenylate cyclase apparently by removing a constraint on receptor-Ns coupling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Animals
  • Cannabinoids / pharmacology
  • Cell Membrane / enzymology
  • Colforsin / pharmacology
  • Dronabinol / pharmacology*
  • Glucagon / pharmacology
  • Guanosine Triphosphate / pharmacology
  • Guanylyl Imidodiphosphate / pharmacology
  • Kinetics
  • Liver / cytology
  • Liver / enzymology*
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, Cell Surface / metabolism*
  • Receptors, Glucagon
  • Sodium Fluoride / pharmacology


  • Cannabinoids
  • Receptors, Cell Surface
  • Receptors, Glucagon
  • Colforsin
  • Guanylyl Imidodiphosphate
  • Dronabinol
  • Guanosine Triphosphate
  • Sodium Fluoride
  • Glucagon
  • Adenylyl Cyclases