Cannabinoid Signaling The cannabinoid receptors CB1 and CB2 can be activated by endogenous, synthetic, and plant cannabinoids. Cayman Chemical offers a broad collection of assay kits, antibodies, and ligands to study these receptors and related enzymes. CB₁-SELECTIVE AGONISTS CB₂-SELECTIVE AGONISTS OH HO CH3 CANNABINOID HO H Cl H H H O O N N N HO N OH H O O O O H O O O O R-1 Arachidonoyl Arachidonoyl N-Arachidonoyl RECEPTORS JWH 133 L-759,633 Tetrahydrocannabivarin HU-308 Methanandamide 2’-Chloroethylamide Cyclopropylamide Dopamine 10 20 CB K = 677 nM CB K = 1,043 nM CB K = 75.4 nM CB K = >10,000 nM CB K = 17.9 - 28.3 nM CB K = 1.4 nM CB K = 2.2 nM CB K = 250 nM 1 i 1 i 1 i 1 i 1 i 1 i 1 i 1 i M K S I L D G L A D T T F R T I T T D L L Y V G S N D I CB K = 3.4 nM CB K = 6.4 nM CB K = 62.8 nM CB K = 22.7 nM CB K = 815 - 868 nM CB K = >2,000 nM CB K = 715 nM CB K = 12,000 nM Q 2 i 2 i 2 i 2 i 2 i 2 i 2 i 2 i Y 30 50 40 O NO E O 2 Q F P S G R F S T L P F K Q P F Y G L K S A M D G K I D 60 E Request a copy of the Cannabinoid N 70 80 10 K N M T A G D N P Q L V P A D Q V N I T E F Y N K S L M E E C W V T E I A N G S K N N F N O O O S D N N 100 90 20 NO2 OH S G N O Cl N C E I D M F N E G C Q I N E E N E K F D K M P N S D L N O F Y N O OH 110 M M 180 N V I N S V C S D I C S E L O Cl L H R M N L H G P L S I Cl 2-Arachidonyl Glycerol AM1235 JWH 073 Q F F N 180 F 370 K K F V 100 T D CB K = 1.5 nM CB K = 8.9 nM K L P S R P ether 1 i 1 i 260 JWH 015 AM1241 LY2828360 GW 405833 P V D K H 270 G L 30 G V D P L T Q CB K = 20.4 nM CB K = 38 nM CB K = 21.2 nM 2 i 2 i CB K = 383 nM CB K = 580 nM CB K = Not reported CB K = 2.04 µM 1 i S H S E I F I P H S C I 270 A V 1 i 1 i 1 i 1 i CB K = >3,000 nM CB K = 13.8 nM CB K = 7.1 nM CB K = 40.3 nM CB K = 14 nM 2 i Q F R C D V K Q F K C P L K 2 i 2 i 2 i 2 i extracellular Q D N N E D T K N A T N S K L I V W T Y V T V V W D H 280 A A F A F F G Y V F F G 190 Y A F I L 190 L V 90 L 170 M L Receptor wall poster at 120 S L M 380 A A S L L M A A F M L F L F CB₁-SELECTIVE ANTAGONISTS/INVERSE AGONISTS V Y K F I V C K S L CB₂-SELECTIVE INVERSE AGONISTS P P C L A I 110 W A C L V L W A 40 C S G 250 L 280 I G L L S 170 360 S F Y L M F V L M T S L Cl L I G G L V V Cl A V S L O T V V L L F O O O O T P L V T I 260 P L V I T V C N N N H C G M A N N N N G S A V S G S L F L L I O T S V L T F 200 O N H N H N H G I W A A W 290 I N F 200 F L L L F L N O N N N O N 130 A L H N T L T L C S T S F C N N H I N L 160 O Cl Cl Cl N S 390 S N Cl I I V L A L I A F A S I N L S T F L 120 S V G N D I T D 80 L M O N 290 E V I E A V W I 50 A W 240 L V L V N G M V N G M I O O Cl Cl Cl Cl N V S Y N L V S L Y V G I V L 160 L P A L T P A C A V 350 A G A SR 144528 AM630 IMMA Rimonabant AM251 AM281 PSNCBAM-1 V L F F Y L I V L L L Y L V L M L L 210 G CB K = 5.6 nM CB K = 7.5 nM CB K = 12 nM CB K = 0.1 µM L A I I CB K = 305 - >10,000 nM CB K = 5,152 nM CB K = >20 µM 1 i 1 i 1 i 1 i C S I Y S T H 250 V 1 i 1 i 1 i G T 210 V Y L G T V L Y 140 Y CB K = 0.3 - 5.6 nM CB K = 31.2 nM CB K = 435 nM CB2 Ki = >1,000 nM CB2 Ki = 2,290 nM CB2 Ki = 4,200 nM CB2 Ki = ≥10 µM V I L V 2 i 2 i 2 i I I A V L V A I I A L L G A 300 www.caymanchem.com/literature I A 150 A L F W L L L F I W L L O H H D K 300 K T R 400 60 S L 130 D R K T R O cytoplasm O S Y R P A K S S Y 70 R G A K S N O N N Cl Cl Cl H R S Y R 230 H A K H S Y R H A G O N O O O O O N S I S L D Q P L T Q L E O H N P T O O O N NC N L O S V C N L R 150 H 340 R L L K H R I N H I I L L H N 220 N N N 2 CF3 R C A I R R R 140 V V R JTE-907 Ridaifen-B H R R A 240 H R P L A Y K V D H Y P P S Y K A D S Cl Cl Cl O Cl 220 CB1 Ki = 2,370 nM CB1 Ki = 732 nM 310 R M S M A L L S CB K = 35.9 nM CB K = 43.7 nM I I I S K Q T G R Q I G S 2 i 2 i R F Q H R A 310 NESS 0327 AM4113 LY320135 Taranabant 320 A D M H 330 R 410 CB K = 0.35 pM CB K = 0.89 nM CB K = 224 nM CB K = 0.13 nM Q R R H 1 i 1 i 1 i 1 i T S E D G K V Q V T R P D S Q V P G M A H M C CB2 Ki = 21 nM CB2 Ki = 92 nM CB2 Ki = >10,000 nM CB2 Ki = 170 nM 230 440 430 420 F 330 320 L S A A N N A H K H L C D S D G M S N D L P Q A T G E C S P S S R P A E E K A E S G L G R V C K K W H A V V 450 460 470 CB₂ RECEPTOR DISTRIBUTION H T R A A E S C I K S T V K I A K V T M S V S T D T S A E A L E T E A D G K I T P W P D S R D L D L S D C CB₁ RECEPTOR DISTRIBUTION 340 350 360 EXPRESSION FUNCTION Immune system (lymph, spleen, thymus, tonsils) · Mediates cytokine release and immune suppression EXPRESSION FUNCTION HUMAN CB1 RECEPTOR HUMAN CB2 RECEPTOR · Leukocytes · Mediates analgesic effects through anti-inflammatory activity Brain (especially on presynaptic GABAergic terminals) · Reduces inhibitory neurotransmission to modulate · T and B lymphocytes · Induces cell migration · Hippocampus cognition, memory, and motor function HUMAN CB & CB altered in mouse, rat S-palmitoylation site toggle switches for G protein binding · Monocytes, macrophages, dendritic cells 1 2 · Regulates phagocytosis · Cerebral cortex · Regulates hypothermia glycosylation sites phosphorylation sites critical role in G & G protein coupling specificity ligand contacts (polar & non-polar)* · Mast cells RECEPTOR KEY s i · Induces apoptosis · Lateral caudate putamen · Modulates dopaminergic reward pathway and addiction Cannabinoid Receptor Antibodies · Substantia nigra pars reticulata · Induces analgesia Neuronal somatodendritic areas (postsynaptic) · Reduces ventral tegmental area neuronal excitability and · Globus pallidus, entopeduncular nucleus cocaine-seeking behavior · Cerebellum MIXED CB₁/CB₂ AGONISTS MIXED CB₁/CB₂ ANTAGONISTS · Modulates hippocampal plasticity and synchronization · Hypothalamus · Substrate for neuroprotection · CNS pain pathways OH Spinal cord, dorsal root ganglion, activated microglia · Modulates neuropathic pain and neuroinflammation OH COOH OH OH OH OH HO H H H H Dorsal horn of spinal cord, primary sensory nerve terminals · Induces analgesia O OH H H H H Vagus nerve · Activates vagal C and/or Aδ fibers N O O OH Item No.