Faculty Collaboration Database

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

Date

08/15/1986

Pubmed ID

3017362

DOI

10.1016/0006-2952(86)90192-9

Scopus ID

2-s2.0-0022505707 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

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.

Author List

Hillard CJ, Bloom AS, Houslay MD

Author

Cecilia J. Hillard PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenylyl Cyclases
Animals
Cannabinoids
Cell Membrane
Colforsin
Dronabinol
Glucagon
Guanosine Triphosphate
Guanylyl Imidodiphosphate
Kinetics
Liver
Male
Rats
Rats, Inbred Strains
Receptors, Cell Surface
Receptors, Glucagon
Sodium Fluoride