EFFECTS OF DELTA-1-TETRAHYDROCANNABINOL ON CYCLIC-AMP IN CULTURED HUMAN-DIPLOID FIBROBLASTS

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 5  (4) , 303-313
Abstract
(-)-trans-.DELTA.1-Tetrahydrocannabinol (.DELTA.1-THC, the major psychoactive component of Cannabis sativa) antagonized the cyclic[c]AMP responses of WI-38 [human embryonic lung] fibroblasts to both prostaglandin E1 (PGE1) and catecholamines. Both cellular cAMP accumulation and cyclic AMP escape to the incubation medium were reduced, but the reduction of escape was much more dramatic at all concentrations of the drug. Long term incubations of cells with .DELTA.1-THC alone resulted in substantial accumulations of cAMP in the incubation medium. This effect was potentiated by the phosphodiesterase inhibitor 1-methyl, 3-isobutylxanthine and appeared to result from weak agonist activity of the cannabinoid determined by stimulation of radioactivity incorporated into cAMP using [3H]adenine prelabeled cells, and a rapid and pronounced increase in the activity ratio of cellular protein kinase. The antagonistic effect of .DELTA.1-THC on the cellular response to PGE1 was greater in preconfluent cells than in confluenct monolayers. The increased sensitivity of preconfluent cultures to .DELTA.1-THC was associated with the appearance of cytoplasmic vacuoles in the perinuclear region of the cells. Cannabidiol acted similar to .DELTA.1-THC in affecting cAMP metabolism whereas cannabinol and cannabicyclol showed mixed effects on the various parameters studied.