INHIBITION OF ADENYLATE-CYCLASE BY DELTA-9-TETRAHYDROCANNABINOL IN MOUSE SPLEEN-CELLS - A POTENTIAL MECHANISM FOR CANNABINOID-MEDIATED IMMUNOSUPPRESSION

The ability of DELTA-9-Tetrahydrocannabinol (DELTA-9-THC) to modulate adenylate cyclase activity in mouse spleen cells was investigated. These studies were prompted by the recent identification and cloning of a G-protein coupled cannabinoid receptor localized in certain regions of the brain and the potential for a common mechanism between cannabinoid-mediated CNS effects and immunosuppression. Temporal addition studies were initially performed to identify the period of time when spleen cells in culture were most susceptible to the inhibitory effects of DELTA-9-THC, as measured by the day 5 IgM antibody forming cell response. DELTA-9-THC was only inhibitory when added to spleen cell cultures during the first 2 hr following antigen sensitization. In light of this time course, adenylate cyclase activity was measured in spleen cells incubated in the presence of 22-mu-M DELTA-9-THC for 5 min and subsequently stimulated with forskolin. DELTA-9-THC treated spleen cells demonstrated a 33% inhibition and a 66% inhibition in intracellular cAMP after a 5 or 15 min stimulation with forskolin, respectively. These studies suggest that inhibition of immune function by DELTA-9-THC may be mediated through the inhibition of intracellular cAMP early after antigen stimulation.