Howlett A C
Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, Missouri 63104, USA.
Neurobiol Dis. 1998 Dec;5(6 Pt B):405-16. doi: 10.1006/nbdi.1998.0215.
The CB1 cannabinoid receptor in brain is a G-protein-coupled receptor that exists as a protein possessing seven transmembrane helices that span the membrane. The intracellular surface is able to interact with f1p4oteins of the Gi/o family to regulate effector proteins, including adenylate cyclase, Ca2+ channels, and K+ channels, and to stimulate the mitogen-activated protein kinase pathway. The CB1 cannabinoid receptor recognizes three classes of agonist ligands: cannabinoid, eicosanoid, and aminoalkylindole. These agonist subtypes may interact with the CB1 cannabinoid receptor by some common points of association, yet may have subtle differences in the way that they interact with the receptor protein. This may be evident in the allosteric regulation by monovalent cations and individual agonists. The juxtamembrane region of the C-terminal is able to activate G-proteins. It is proposed that conformational changes in the receptor induced by agonist ligands may alter the conformation or exposure of the juxtamembrane C-terminal region extending from helix VII.
大脑中的CB1大麻素受体是一种G蛋白偶联受体,以一种具有七个跨膜螺旋且贯穿细胞膜的蛋白质形式存在。细胞内表面能够与Gi/o家族的蛋白质相互作用,以调节效应蛋白,包括腺苷酸环化酶、Ca2+通道和K+通道,并刺激丝裂原活化蛋白激酶途径。CB1大麻素受体识别三类激动剂配体:大麻素、类花生酸和氨基烷基吲哚。这些激动剂亚型可能通过一些共同的结合点与CB1大麻素受体相互作用,但在与受体蛋白相互作用的方式上可能存在细微差异。这在单价阳离子和个别激动剂的变构调节中可能很明显。C末端的近膜区域能够激活G蛋白。有人提出,激动剂配体诱导的受体构象变化可能会改变从螺旋VII延伸的近膜C末端区域的构象或暴露情况。