Prostaglandins and cannabis. XII. The effect of cannabinoid structure on the synthesis of prostaglandins by human lung fibroblasts.
Earlier findings indicated that several other cannabinoids in addition to delta 1-tetrahydro-cannabinol (THC) were able to stimulate the synthesis of prostaglandins in cell culture systems. The present study was initiated to delineate the structural requirements for this effect within the cannabinoid series. Among the primary cannabinoids, we found that the trend was for more planar structures to show greater activity. In the case of THC metabolites, the order of activity was delta 1-THC greater than 7-oxo-delta 1, 6-THC greater than 7-OH-delta 1-THC greater than 3"-OH-delta 1-THC = 6 beta-OH-delta 1-THC = 6 alpha-OH-delta 1-THC greater than delta 1, 6-THC-7-oic acid. The latter sequence compares favorably with the available data on the behavioral assay in the rhesus monkey and the subjective "high" in humans. We also observed a good correlation between the release of arachidonic acid and the production of prostaglandin E, over a series of eight cannabinoids. This gives further support that the site of action in this effect is the elevation of activity of the phospholipase(s) responsible for supplying precursor arachidonic acid for prostaglandin synthesis.
D001095:Arachidonic Acids / Q000378:metabolism; D002186:Cannabinoids / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005333:Fetus; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D013329:Structure-Activity Relationship
D001095:Arachidonic Acids; D002186:Cannabinoids; D011453:Prostaglandins; D011458:Prostaglandins E