Signal Transduction via Cannabinoid Receptors

被引:69
作者
Dalton, George D. [1 ]
Bass, Caroline E. [1 ]
Van Horn, Cynthia G. [1 ]
Howlett, Allyn C. [1 ]
机构
[1] Wake Forest Univ Hlth Sci, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA
关键词
Anandamide; 2-arachidonoylglycerol; cannabinoid receptor heteromers; endocannabinoid; extracellular signal-regulated kinase; G-proteins; receptor tyrosine kinases; peroxisome proliferator-activated receptor; MU-OPIOID-RECEPTORS; ACTIVATED PROTEIN-KINASE; HEPATIC CB1 RECEPTORS; ACID AMIDE HYDROLASE; MORPHINE-TOLERANCE; CALCIUM-CHANNELS; MITOCHONDRIAL BIOGENESIS; PHARMACOLOGICAL ACTIONS; CONCURRENT STIMULATION; ENDOCANNABINOID SYSTEM;
D O I
10.2174/187152709789824615
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The endocannabinoids anandamide and 2-arachidonoylglycerol are lipid mediators that signal via CB1 and CB2 cannabinoid receptors and Gi/o-proteins to inhibit adenylyl cyclase and stimulate mitogen-activated protein kinase. In the brain, CB1 receptors interact with opioid receptors in close proximity, and these receptors may share G-proteins and effector systems. In the striatum, CB1 receptors function in coordination with D-1 and D-2 dopamine receptors, and combined stimulation of CB1-D-2 receptor heteromeric complexes promotes a unique interaction to stimulate cAMP production. CB1 receptors also trigger growth factor receptor signaling cascades in cells by engaging in cross-talk or inter-receptor signal transmission with the receptor tyrosine kinase (RTK) family. Mechanisms for CB1 receptor-RTK transactivation can include stimulation of signal transduction pathways regulated by second messengers as well as phospholipase C, metalloprotease cleavage of membrane-bound precursor proteins such as epidermal growth factor which activate RTKs, RTK autophosphorylation, and recruitment of non-receptor tyrosine kinases. CB1 and CB2 receptors are expressed in peripheral tissues including liver and adipose tissue, and are induced in pathological conditions. Novel signal transduction resulting from endocannabinoid regulation of AMP-regulated kinase and peroxisome proliferator-activated receptors have been discovered from studies of hepatocytes and adipocytes. It can be predicted that drug discovery of the future will be based upon these novel signal transduction mechanisms for endocannabinoid mediators.
引用
收藏
页码:422 / 431
页数:10
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