Reichman M, Nen W, Hokin L E
Department of Pharmacology, University of Wisconsin Medical School, Madison 53706.
Mol Pharmacol. 1987 Nov;32(5):686-90.
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.
为了研究大麻素对哺乳动物中枢神经系统中前列腺素（PG）形成的影响，从豚鼠脑的不同区域制备切片，并与（-）-反式-Δ⁹-四氢大麻酚（THC）一起孵育，同时加入或不加入乙酰胆碱（ACh）。通过放射免疫测定法测量释放到培养基中的前列腺素E（PGE）和前列腺素F（PGF）的量。用浓度范围为0.8 - 16微摩尔/升的THC孵育大脑皮层切片1小时，可显著抑制PGE和PGF的形成，抑制程度高达对照水平的50%。用具有精神活性的THC同系物Δ⁸-THC孵育皮层切片，导致PGE和PGF水平出现类似的剂量依赖性抑制。缺乏精神活性的THC同系物，即大麻二酚和THC的无活性立体异构体，对PGE合成的抑制作用较弱。与具有精神活性的大麻素的抑制作用形成鲜明对比的是，在无精神活性的同系物存在下，PGF水平升高。比较了THC在不同脑区对PG形成的影响。在纹状体切片中，0.8微摩尔/升的THC显著刺激PG形成，但对小脑的PG水平没有影响。为了深入了解THC与内源性神经递质之间的相互作用，我们比较了THC对大脑皮层和小脑皮层中ACh诱导的PG形成增加的影响。在大脑皮层中，0.8微摩尔/升的THC消除了ACh诱导的PGE水平升高，并将PGF的升高抑制了70%。相比之下，THC对小脑皮层中ACh诱导的PG水平升高没有显著影响。结果表明，大麻素改变了大脑中PGE和PGF的基础形成以及ACh增强的形成过程，并且这些作用在结构和区域上具有特异性。
