Endocannabinoid transporter

The endocannabinoid transporters (eCBTs) are transport proteins for the endocannabinoids. Most neurotransmitters are water-soluble and require transmembrane proteins to transport them across the cell membrane. The endocannabinoids (anandamide, AEA, and 2-arachidonoylglycerol, 2-AG) on the other hand, are non-charged lipids that readily cross lipid membranes.[1][2][3][4][5] However, since the endocannabinoids are water immiscible, protein transporters have been described that act as carriers to solubilize and transport the endocannabinoids through the aqueous cytoplasm. These include the heat shock proteins (Hsp70s) and fatty acid binding proteins for anandamide (FABPs).[6][7] FABPs such as FABP1, FABP3, FABP5, and FABP7 have been shown to bind endocannabinoids.[8][9] FABP inhibitors attenuate the breakdown of anandamide by the enzyme fatty acid amide hydrolase (FAAH) in cell culture.[6] One of these inhibitors (SB-FI-26), isolated from a virtual library of a million compounds, belongs to a class of compounds (named the "truxilloids') that act as an anti-nociceptive agent with mild anti-inflammatory activity in mice.[10] These truxillic acids and their derivatives have been known to have anti-inflammatory and anti-nociceptive effects in mice[11] and are active components of a Chinese herbal medicine ((−)-Incarvillateine Incarvillea sinensis) used to treat rheumatism and pain in human. The blockade of anandamide transport may, at least in part, be the mechanism through which these compounds exert their anti-nociceptive effects.

See also

References

  1. ↑ Kaczocha, Martin; Lin, Qingqing; Nelson, Lindsay D.; McKinney, Michelle K.; Cravatt, Benjamin F.; London, Erwin; Deutsch, Deutsch (2012). "Anandamide Externally Added to Lipid Vesicles Containing-Trapped Fatty Acid Amide Hydrolase (FAAH) Is Readily Hydrolyzed in a Sterol-Modulated Fashion". ACS Chemical Neuroscience. 3 (5): 364–368. PMC 3382455 Freely accessible. PMID 22860204. doi:10.1021/cn300001w.
  2. ↑ Bojesen, Inge N.; Hansen, Harald S. (2005). "Membrane transport of anandamide through resealed human red blood cell membranes". The Journal of Lipid Research. 46 no. (8): 1652–1659. doi:10.1194/jlr.M400498-JLR200.
  3. ↑ Kaczocha, Martin; Hermann, Anita; Glaser, Sherrye T.; Bojesen, Inge N.; Deutsch, Dale G. (2006). "Anandamide Uptake Is Consistent with Rate-limited Diffusion and Is Regulated by the Degree of Its Hydrolysis by Fatty Acid Amide Hydrolase". The Journal of Biological Chemistry. 281 (14): 9066–9075. PMID 16461355. doi:10.1074/jbc.M509721200.
  4. ↑ Sandberg, A.; Fowler, C.J. (2005). "Measurement of saturable and non-saturable components of anandamide uptake into P19 embryonic carcinoma cells in the presence of fatty acid-free bovine serum albumin.". Chemistry and Physics of Lipids. 134 (2): 131–139. PMID 15784231. doi:10.1016/j.chemphyslip.2004.12.010.
  5. ↑ Di Pasquale, E.; Chahinian, H.; Sanchez, P.; Fantini, J. (2009). "The Insertion and Transport of Anandamide in Synthetic Lipid Membranes Are Both Cholesterol-Dependent" [Translated title]. PLoS ONE. 4 (3): e4989. PMC 2658885 Freely accessible. PMID 19330032. doi:10.1371/journal.pone.0004989.
  6. 1 2 Kaczocha, M.; Glaser, S.T.; Deutsch, D.G. (2009). "Identification of intracellular carriers for the endocannabinoid anandamide". Proceedings of the National Academy of Sciences of the United States of America. 106 (15): 6375–6380. PMC 2669397 Freely accessible. PMID 19307565. doi:10.1073/pnas.0901515106.
  7. ↑ Oddi, S.; Fezza, F.; Pasquariello, N.; D'Agostino, A.; Catanzaro, G.; De Simone, C.; Rapino, C.; Finazzi-Agro, A.; Maccarrone, M. (2009). "Molecular identification of albumin and Hsp70 as cytosolic anandamide-binding proteins". Chemistry & Biology. 16 (6): 624–632. PMID 19481477. doi:10.1016/j.chembiol.2009.05.004.
  8. ↑ Huang, Huan; McIntosh, Avery L.; Martin, Gregory G.; Landrock, Danilo; Chung, Sarah; Landrock, Kerstin K.; Dangott, Lawrence J.; Li, Shengrong; Kier, Ann B. (2016-09-20). "FABP1: A Novel Hepatic Endocannabinoid and Cannabinoid Binding Protein". Biochemistry. 55 (37): 5243–5255. ISSN 0006-2960. PMID 27552286. doi:10.1021/acs.biochem.6b00446.
  9. ↑ Elmes, Matthew W.; Kaczocha, Martin; Berger, William T.; Leung, KwanNok; Ralph, Brian P.; Wang, Liqun; Sweeney, Joseph M.; Miyauchi, Jeremy T.; Tsirka, Stella E. (2015-04-03). "Fatty Acid-binding Proteins (FABPs) Are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD)". Journal of Biological Chemistry. 290 (14): 8711–8721. ISSN 0021-9258. PMC 4423662 Freely accessible. PMID 25666611. doi:10.1074/jbc.M114.618447.
  10. ↑ Berger, W.T.; Ralph, B.P.; Kaczocha, M.; Sun, J.; Balius, T.E.; Rizzo, R.C.; Haj-Dahmane, S.; Ojima, I.; Deutsch, D.G. (2012). "Targeting Fatty Acid Binding Protein (FABP) Anandamide Transporters – A Novel Strategy for Development of Anti-Inflammatory and Anti-Nociceptive Drugs". PLoS ONE. 7 (12): e50968. PMC 3517626 Freely accessible. PMID 23236415. doi:10.1371/journal.pone.0050968.
  11. ↑ Nakamura, M.; Chi, Y.M.; Yan, W.M.; Nakasugi, Y.; Yoshizawa, T.; Irino, N.; Hashimoto, F.; Kinjo, J.; Nahara, T.; Sakurada, S. (1999). "Strong antinociceptive effect of incarvillateine, a novel monoterpene alkaloid from Incarvillea sinensis". Journal of Natural Products. 62 (9): 1293–1294. PMID 10514316. doi:10.1021/np990041c.


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