Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33314, USA.
Int J Mol Sci. 2020 Oct 17;21(20):7693. doi: 10.3390/ijms21207693.
The identification of the human cannabinoid receptors and their roles in health and disease, has been one of the most significant biochemical and pharmacological advancements to have occurred in the past few decades. In spite of the major strides made in furthering endocannabinoid research, therapeutic exploitation of the endocannabinoid system has often been a challenging task. An impaired endocannabinoid tone often manifests as changes in expression and/or functions of type 1 and/or type 2 cannabinoid receptors. It becomes important to understand how alterations in cannabinoid receptor cellular signaling can lead to disruptions in major physiological and biological functions, as they are often associated with the pathogenesis of several neurological, cardiovascular, metabolic, and inflammatory diseases. This review focusses mostly on the pathophysiological roles of type 1 and type 2 cannabinoid receptors, and it attempts to integrate both cellular and physiological functions of the cannabinoid receptors. Apart from an updated review of pre-clinical and clinical studies, the adequacy/inadequacy of cannabinoid-based therapeutics in various pathological conditions is also highlighted. Finally, alternative strategies to modulate endocannabinoid tone, and future directions are also emphasized.
鉴定人类大麻素受体及其在健康和疾病中的作用是过去几十年中发生的最重要的生化和药理学进展之一。尽管在进一步研究内源性大麻素方面取得了重大进展，但内源性大麻素系统的治疗利用常常是一项具有挑战性的任务。内源性大麻素张力的减弱常常表现为 1 型和/或 2 型大麻素受体表达和/或功能的改变。了解大麻素受体细胞信号转导的改变如何导致主要生理和生物学功能的紊乱变得尤为重要，因为这些改变常常与几种神经、心血管、代谢和炎症性疾病的发病机制有关。这篇综述主要集中在 1 型和 2 型大麻素受体的病理生理学作用上，并试图整合大麻素受体的细胞和生理功能。除了对临床前和临床研究的最新综述外，还强调了大麻素类药物在各种病理情况下的充分性/不足性。最后，还强调了调节内源性大麻素张力的替代策略和未来方向。
