Cannabinoid receptors. Receptors are proteins, and proteins are made up of strings of amino acids. Each circle in the diagram represents one amino acid. The shaded bar represents the cell membrane, which like all cell membranes in animals is composed largely of phospholipids. Like many receptors, the cannabinoid receptors span the cell membrane; some sections of the receptor protein are outside the cell membrane (extracellular); some are inside (intracellular). THC, anandamide, and other known cannabinoid receptor agonists bind to the extracellular portion of the receptor, thereby activating the signal pathway inside the cell. The CB1 molecule is larger than CB2. The receptor molecules are most similar in four of the seven regions where they are embedded in the cell membrane (known as the transmembrane regions). The intracellular loops of the two receptor subtypes are quite different, which might affect the cellular response to the ligand because these loops are known to mediate G protein signaling, the next step in the cell signaling pathway after the receptor. Receptor homology between the two receptor subtypes is 44% for the full-length protein and 68% within the seven transmembrane regions. The ligand binding sites are typically defined by the extracellular loops and the transmembrane regions.
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