Prostaglandins and cannabis XV. Comparison of enantiomeric cannabinoids in stimulating prostaglandin synthesis in fibroblasts.
Stereospecificity has been reported for a number of actions of the cannabinoids in a variety of systems. In the present report, we have shown that this effect can also be demonstrated when human lung fibroblasts in monolayer culture are stimulated by cannabinoids to produce prostaglandin E2 (PGE2). Three enantiomeric pairs of cannabinoids, (+) and (-)-delta 1-tetrahydrocannabinol (THC), (+) and (-)-delta 6-THC and (+) and (-)-delta 6-dimethylheptyl (DMH) THC were tested. In each case the (-) isomer was significantly more potent in agreement with the findings of others using different systems. Interestingly, very little stereospecificity was found in fibroblasts when the release of arachidonic acid, the precursor of PGE2, was monitored. This suggests that cannabinoids may act at several sites within the cell some of which show comparatively greater stereoselectivity for these agonists.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D002186:Cannabinoids / Q000494:pharmacology*; D002460:Cell Line; D015232:Dinoprostone; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001095:Arachidonic Acids; D002186:Cannabinoids; D008051:Lipid Bilayers; D011458:Prostaglandins E; C033189:dimethyl-heptyl tetrahydrocannabinol; D016718:Arachidonic Acid; D013759:Dronabinol; D015232:Dinoprostone