Department of Psychological and Brain Sciences, Gill Center for Biomolecular Science, Indiana University, Bloomington, IN 47405, USA.
Br J Pharmacol. 2012 Apr;165(8):2660-71. doi: 10.1111/j.1476-5381.2011.01744.x.
Cannabinoids such as Δ(9) - tetrahydrocannabinol, the major psychoactive component of marijuana and hashish, primarily act via cannabinoid CB(1) and CB(2) receptors to produce characteristic behavioural effects in humans. Due to the tractability of rodent models for electrophysiological and behavioural studies, most of the studies of cannabinoid receptor action have used rodent cannabinoid receptors. While CB(1) receptors are relatively well-conserved among mammals, human CB(1) (hCB(1) ) differs from rCB(1) and mCB(1) receptors at 13 residues, which may result in differential signalling. In addition, two hCB(1) splice variants (hCB(1a) and hCB(1b) ) have been reported, diverging in their amino-termini relative to hCB(1) receptors. In this study, we have examined hCB(1) signalling in neurones.
hCB(1) , hCB(1a) hCB(1b) or rCB(1) receptors were expressed in autaptic cultured hippocampal neurones from CB(1) (-/-) mice. Such cells express a complete endogenous cannabinoid signalling system. Electrophysiological techniques were used to assess CB(1) receptor-mediated signalling. KEY RESULTS Expressed in autaptic hippocampal neurones cultured from CB(1) (-/-) mice, hCB(1) , hCB(1a) and hCB(1b) signal differentially from one another and from rodent CB(1) receptors. Specifically, hCB(1) receptors inhibit synaptic transmission less effectively than rCB(1) receptors.
Our results suggest that cannabinoid receptor signalling in humans is quantitatively very different from that in rodents. As the problems of marijuana and hashish abuse occur in humans, our results highlight the importance of studying hCB(1) receptors. They also suggest further study of the distribution and function of hCB(1) receptor splice variants, given their differential signalling and potential impact on human health.
This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.
大麻和哈希什中的主要精神活性成分 Δ(9)-四氢大麻酚等大麻素主要通过大麻素 CB(1)和 CB(2)受体发挥作用，在人类中产生特征性行为效应。由于啮齿动物模型在电生理和行为研究方面具有可操作性，因此大多数关于大麻素受体作用的研究都使用了啮齿动物大麻素受体。虽然 CB(1)受体在哺乳动物中相对保守，但人类 CB(1)（hCB(1)）与 rCB(1)和 mCB(1)受体在 13 个残基处存在差异，这可能导致信号转导不同。此外，已经报道了两种 hCB(1)剪接变体（hCB(1a)和 hCB(1b)），它们相对于 hCB(1)受体在氨基末端上有所不同。在这项研究中，我们检查了神经元中的 hCB(1)信号。
在来自 CB(1)(-/-)小鼠的自突触培养海马神经元中表达 hCB(1)、hCB(1a)、hCB(1b)或 rCB(1)受体。这样的细胞表达完整的内源性大麻素信号系统。使用电生理技术评估 CB(1)受体介导的信号转导。
在来自 CB(1)(-/-)小鼠的自突触培养海马神经元中表达的 hCB(1)、hCB(1a)和 hCB(1b)彼此之间以及与啮齿动物 CB(1)受体的信号不同。具体而言，hCB(1)受体对突触传递的抑制作用不如 rCB(1)受体有效。
我们的结果表明，人类大麻素受体信号在数量上与啮齿动物有很大不同。由于大麻和哈希什滥用问题发生在人类中，我们的结果强调了研究 hCB(1)受体的重要性。鉴于 hCB(1)受体剪接变体的信号差异及其对人类健康的潜在影响，它们还表明需要进一步研究 hCB(1)受体剪接变体的分布和功能。
本文是关于大麻素在生物学和医学中的主题部分的一部分。要查看该部分中的其他文章，请访问 http://dx.doi.org/10.1111/bph.2012.165.issue-8。要查看大麻素在生物学和医学中的第一部分，请访问 http://dx.doi.org/10.1111/bph.2011.163.issue-7。
