Munro S, Thomas K L, Abu-Shaar M
MRC Laboratory of Molecular Biology, Cambridge, UK.
Nature. 1993 Sep 2;365(6441):61-5. doi: 10.1038/365061a0.
The major active ingredient of marijuana, delta 9-tetrahydrocannabinol (delta 9-THC), has been used as a psychoactive agent for thousands of years. Marijuana, and delta 9-THC, also exert a wide range of other effects including analgesia, anti-inflammation, immunosuppression, anticonvulsion, alleviation of intraocular pressure in glaucoma, and attenuation of vomiting. The clinical application of cannabinoids has, however, been limited by their psychoactive effects, and this has led to interest in the biochemical bases of their action. Progress stemmed initially from the synthesis of potent derivatives of delta 9-THC, and more recently from the cloning of a gene encoding a G-protein-coupled receptor for cannabinoids. This receptor is expressed in the brain but not in the periphery, except for a low level in testes. It has been proposed that the nonpsychoactive effects of cannabinoids are either mediated centrally or through direct interaction with other, non-receptor proteins. Here we report the cloning of a receptor for cannabinoids that is not expressed in the brain but rather in macrophages in the marginal zone of spleen.
大麻的主要活性成分Δ9-四氢大麻酚（Δ9-THC）作为一种精神活性物质已被使用了数千年。大麻和Δ9-THC还具有广泛的其他作用，包括镇痛、抗炎、免疫抑制、抗惊厥、降低青光眼的眼压以及减轻呕吐。然而，大麻素的临床应用因其精神活性作用而受到限制，这引发了人们对其作用生化基础的兴趣。最初的进展源于Δ9-THC强效衍生物的合成，最近则来自编码大麻素G蛋白偶联受体基因的克隆。该受体在大脑中表达，但在外周组织中不表达，睾丸中仅有低水平表达。有人提出，大麻素的非精神活性作用要么是通过中枢介导，要么是通过与其他非受体蛋白的直接相互作用来实现。在此，我们报告克隆了一种大麻素受体，该受体不在大脑中表达，而是在脾脏边缘区的巨噬细胞中表达。
