Effects of delta 9-tetrahydrocannabinol on prostaglandin formation in brain.
In order to investigate the effects of cannabinoids on prostaglandin (PG) formation in the mammalian central nervous system, slices were prepared from different regions of guinea pig brain and incubated with (-)-trans-delta 9-tetrahydrocannabinol (THC) with or without acetylcholine (ACh). The amounts of prostaglandins E (PGE) and (F (PGF) released into the medium were measured by radioimmunoassay. Incubation of cerebral cortex slices for 1 hr with concentrations of THC over the range of 0.8-16 microM significantly inhibited the formation of both PGE and PGF by up to 50% of control levels. Incubation of cortical slices with delta 8-THC, a psychoactive THC congener, resulted in similar dose-dependent inhibitions in both PGE and PGF levels. Congeners of THC devoid of psychoactivity, namely, cannabidiol and the inactive stereoisomer of THC, were less potent inhibitors of PGE synthesis. In marked contrast to the inhibitory effect of the psychoactive cannabinoids, PGF levels were elevated in the presence of the nonpsychoactive congeners. The effects of THC on PG formation were compared in different brain regions. In striatal slices, 0.8 microM THC significantly stimulated PG formation but did not affect PG levels in the cerebellum. In order to gain insight into the interaction between THC and endogenous neurotransmitters, we compared the effect of THC on the ACh-induced increase in PG formation in the cerebral cortex and the cerebellar cortex. In the cerebral cortex, 0.8 microM THC abolished the ACh-induced increase in PGE levels and inhibited the rise in PGF by 70%. In contrast, THC did not significantly affect the ACh-induced rise in PG levels in the cerebellum. The results indicate that cannabinoids alter both the basal and ACh-enhanced formation of PGE and PGF in the brain and that these effects are structurally and regionally specific.
Reichman
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Department of Pharmacology, University of Wisconsin Medical School, Madison 53706.
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Hokin
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002185:Cannabidiol / Q000494:pharmacology; D013759:Dronabinol / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009928:Organ Specificity; D011453:Prostaglandins / Q000096:biosynthesis*; D013237:Stereoisomerism
D011453:Prostaglandins; D002185:Cannabidiol; D013759:Dronabinol; D000109:Acetylcholine