N-Arachidonoyl dopamine
Chemical compound
Names | |
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Preferred IUPAC name
(5
Z
,8
Z
,11
Z
,14
Z
)-
N
-[2-(3,4-Dihydroxyphenyl)ethyl]icosa-5,8,11,14-tetraenamide
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Other names
NADA
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Identifiers | |
3D model (
JSmol
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ChEMBL | |
ChemSpider |
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PubChem
CID
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CompTox Dashboard
(
EPA
)
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Properties | |
C 28 H 41 NO 3 | |
Molar mass | 439.63 g/mol |
Except where otherwise noted, data are given for materials in their
standard state
(at 25
°C [77
°F], 100
kPa).
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N -Arachidonoyl dopamine ( NADA ) is an endocannabinoid that acts as an agonist of the CB 1 receptor and the transient receptor potential V1 (TRPV1) ion channel . NADA was first described as a putative endocannabinoid (agonist for the CB 1 receptor) in 2000 [1] and was subsequently identified as an endovanilloid (agonist for TRPV1) in 2002. [2] NADA is an endogenous arachidonic acid based lipid found in the brain of rats, with especially high concentrations in the hippocampus , cerebellum , and striatum . [2] It activates the TRPV1 channel with an EC 50 of approximately of 50 nM which makes it the putative endogenous TRPV1 agonist. [2]
In mice, NADA was shown to induce the tetrad of physiological paradigms associated with cannabinoids: hypothermia, hypo-locomotion, catalepsy, and analgesia. [1] [3] [4] NADA has been found to play a regulatory role in both the peripheral and central nervous systems, and displays antioxidant and neuroprotectant properties. [2] [5] [6] [7] NADA has also been implicated in smooth muscle contraction and vasorelaxation in blood vessels. [8] [9] [10] [11] Additionally, NADA has been observed to suppress inflammatory activation of human Jurkat T cells and to inhibit the release of prostaglandin E2 (PGE2) from lipopolysaccharide (LPS)-activated astrocytes, microglia and mouse brain ECs (MEC-Brain). [12] [13] [14] NADA also promotes the inflammatory resolution of human endothelial cells activated by both endogenous ( i.e. TNF) and exogenous ( i.e. bacterial derived LPS (TLR4 agonist) and FSL-1 (TLR2/6 agonist)) inflammatory mediators. [15] It can increase the TRPV1-mediated release of substance P and calcitonin gene-related peptide (CGRP) in rat dorsal spinal cord slices. [2] Furthermore, NADA also displays inhibitory activity in HIV-1 replication assays. [16] Finally, NADA can prevent the degranulation and release of TNF from RBL- 2H3 mast cells treated with an IgE-antigen complex. [17] Together, these studies show that physiological functions attributed to NADA are multifaceted, and include the ability to modulate the immune response.
The biosynthetic pathway of N-arachindonoyldopamine is not well understood. It has been proposed to be conjugated from arachidonoyl-CoA or arachidonoyl phospholipids and dopamine, but in vitro experiments do not support this theory. [18] However, the indirect biosynthesis of phospholipid esters with dopamine may be possible, as dopamine can induce the aminolysis of the glycerol-fatty acid bonds in phospholipid chains (arachidonoyl, palmitoyl, linoleyl, etc.). [19]
See also
References
- 1 2 Bisogno, T.; Melck, D.; Bobrov MYu, null; Gretskaya, N. M.; Bezuglov, V. V.; De Petrocellis, L.; Di Marzo, V. (2000-11-01). "N-acyl-dopamines: novel synthetic CB(1) cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo" . The Biochemical Journal . 351 (3): 817–824. doi : 10.1042/bj3510817 . ISSN 0264-6021 . PMC 1221424 . PMID 11042139 .
- 1 2 3 4 5 Huang, Susan M.; Bisogno, Tiziana; Trevisani, Marcello; Al-Hayani, Abdulmonem; Petrocellis, Luciano De; Fezza, Filomena; Tognetto, Michele; Petros, Timothy J.; Krey, Jocelyn F.; Chu, Constance J.; Miller, Jeffrey D.; Davies, Stephen N.; Geppetti, Pierangelo; Walker, J. Michael; Marzo, Vincenzo Di (2002-06-11). "An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors" . Proceedings of the National Academy of Sciences of the United States of America . 99 (12): 8400–8405. Bibcode : 2002PNAS...99.8400H . doi : 10.1073/pnas.122196999 . PMC 123079 . PMID 12060783 .
- ↑ Bezuglov, V.; Bobrov, M.; Gretskaya, N.; Gonchar, A.; Zinchenko, G.; Melck, D.; Bisogno, T.; Di Marzo, V.; Kuklev, D. (2001-02-26). "Synthesis and biological evaluation of novel amides of polyunsaturated fatty acids with dopamine". Bioorganic & Medicinal Chemistry Letters . 11 (4): 447–449. doi : 10.1016/s0960-894x(00)00689-2 . ISSN 0960-894X . PMID 11229744 .
- ↑ Little, P. J.; Compton, D. R.; Johnson, M. R.; Melvin, L. S.; Martin, B. R. (1988-12-01). "Pharmacology and stereoselectivity of structurally novel cannabinoids in mice". The Journal of Pharmacology and Experimental Therapeutics . 247 (3): 1046–1051. ISSN 0022-3565 . PMID 2849657 .
- ↑ Price, Theodore J.; Patwardhan, Amol; Akopian, Armen N.; Hargreaves, Kenneth M.; Flores, Christopher M. (2004-04-01). "Modulation of trigeminal sensory neuron activity by the dual cannabinoid-vanilloid agonists anandamide, N-arachidonoyl-dopamine and arachidonyl-2-chloroethylamide" . British Journal of Pharmacology . 141 (7): 1118–1130. doi : 10.1038/sj.bjp.0705711 . ISSN 0007-1188 . PMC 1574881 . PMID 15006899 .
- ↑ Marinelli, Silvia; Di Marzo, Vincenzo; Florenzano, Fulvio; Fezza, Filomena; Viscomi, Maria Teresa; van der Stelt, Mario; Bernardi, Giorgio; Molinari, Marco; Maccarrone, Mauro (2007-02-01). "N-arachidonoyl-dopamine tunes synaptic transmission onto dopaminergic neurons by activating both cannabinoid and vanilloid receptors" . Neuropsychopharmacology . 32 (2): 298–308. doi : 10.1038/sj.npp.1301118 . ISSN 0893-133X . PMID 16760924 .
- ↑ Sagar, Devi R.; Smith, Paul A.; Millns, Paul J.; Smart, Darren; Kendall, David A.; Chapman, Victoria (2004-07-01). "TRPV1 and CB(1) receptor-mediated effects of the endovanilloid/endocannabinoid N-arachidonoyl-dopamine on primary afferent fibre and spinal cord neuronal responses in the rat". The European Journal of Neuroscience . 20 (1): 175–184. doi : 10.1111/j.1460-9568.2004.03481.x . ISSN 0953-816X . PMID 15245490 . S2CID 42626601 .
- ↑ Bobrov, Mikhail Yu; Lizhin, Anatoly A.; Andrianova, Ekaterina L.; Gretskaya, Natalia M.; Frumkina, Lidia E.; Khaspekov, Leonid G.; Bezuglov, Vladimir V. (2008-01-24). "Antioxidant and neuroprotective properties of N-arachidonoyldopamine". Neuroscience Letters . 431 (1): 6–11. doi : 10.1016/j.neulet.2007.11.010 . ISSN 0304-3940 . PMID 18069125 . S2CID 23436811 .
- ↑ Harrison, Selena; De Petrocellis, Luciano; Trevisani, Marcello; Benvenuti, Francesca; Bifulco, Maurizio; Geppetti, Pierangelo; Di Marzo, Vincenzo (2003-08-15). "Capsaicin-like effects of N-arachidonoyl-dopamine in the isolated guinea pig bronchi and urinary bladder". European Journal of Pharmacology . 475 (1–3): 107–114. doi : 10.1016/s0014-2999(03)02114-9 . ISSN 0014-2999 . PMID 12954366 .
- ↑ O'Sullivan, Saoirse E.; Kendall, David A.; Randall, Michael D. (2004-03-01). "Characterisation of the vasorelaxant properties of the novel endocannabinoid N-arachidonoyl-dopamine (NADA)" . British Journal of Pharmacology . 141 (5): 803–812. doi : 10.1038/sj.bjp.0705643 . ISSN 0007-1188 . PMC 1574254 . PMID 14769783 .
- ↑ O'Sullivan, Saoirse E.; Kendall, David A.; Randall, Michael D. (2009-01-01). "Time-dependent vascular effects of Endocannabinoids mediated by peroxisome proliferator-activated receptor gamma (PPARγ)" . PPAR Research . 2009 : 425289. doi : 10.1155/2009/425289 . ISSN 1687-4757 . PMC 2676321 . PMID 19421417 .
- ↑ Navarrete, Carmen M.; Fiebich, Bernd L.; de Vinuesa, Amaya García; Hess, Sandra; de Oliveira, Antonio C. P.; Candelario-Jalil, Eduardo; Caballero, Francisco J.; Calzado, Marco A.; Muñoz, Eduardo (2009-04-01). "Opposite effects of anandamide and N-arachidonoyl dopamine in the regulation of prostaglandin E and 8-iso-PGF formation in primary glial cells". Journal of Neurochemistry . 109 (2): 452–464. doi : 10.1111/j.1471-4159.2009.05966.x . ISSN 1471-4159 . PMID 19200337 . S2CID 205620351 .
- ↑ Navarrete, Carmen M.; Pérez, Moisés; de Vinuesa, Amaya García; Collado, Juan A.; Fiebich, Bernd L.; Calzado, Marco A.; Muñoz, Eduardo (2010-06-15). "Endogenous N-acyl-dopamines induce COX-2 expression in brain endothelial cells by stabilizing mRNA through a p38 dependent pathway". Biochemical Pharmacology . 79 (12): 1805–1814. doi : 10.1016/j.bcp.2010.02.014 . ISSN 1873-2968 . PMID 20206142 .
- ↑ Sancho, Rocío; Macho, Antonio; de La Vega, Laureano; Calzado, Marco A.; Fiebich, Bernd L.; Appendino, Giovanni; Muñoz, Eduardo (2004-02-15). "Immunosuppressive activity of endovanilloids: N-arachidonoyl-dopamine inhibits activation of the NF-kappa B, NFAT, and activator protein 1 signaling pathways" . Journal of Immunology . 172 (4): 2341–2351. doi : 10.4049/jimmunol.172.4.2341 . ISSN 0022-1767 . PMID 14764703 .
- ↑ Wilhelmsen, Kevin; Khakpour, Samira; Tran, Alphonso; Sheehan, Kayla; Schumacher, Mark; Xu, Fengyun; Hellman, Judith (2014-05-09). "The endocannabinoid/endovanilloid N-arachidonoyl dopamine (NADA) and synthetic cannabinoid WIN55,212-2 abate the inflammatory activation of human endothelial cells" . The Journal of Biological Chemistry . 289 (19): 13079–13100. doi : 10.1074/jbc.M113.536953 . ISSN 1083-351X . PMC 4036321 . PMID 24644287 .
- ↑ Sancho, Rocío; de la Vega, Laureano; Macho, Antonio; Appendino, Giovanni; Di Marzo, Vincenzo; Muñoz, Eduardo (2005-09-15). "Mechanisms of HIV-1 inhibition by the lipid mediator N-arachidonoyldopamine" . Journal of Immunology . 175 (6): 3990–3999. doi : 10.4049/jimmunol.175.6.3990 . ISSN 0022-1767 . PMID 16148147 .
- ↑ Yoo, Jae-Myung; Park, Eun Seok; Kim, Mee Ree; Sok, Dai-Eun (2013-04-01). "Inhibitory effect of N-Acyl dopamines on IgE-mediated allergic response in RBL-2H3 cells". Lipids . 48 (4): 383–393. doi : 10.1007/s11745-013-3758-6 . ISSN 1558-9307 . PMID 23377981 . S2CID 3995567 .
- ↑ Shu-Jung Hu, Sherry; Bradshaw, Heather B.; Benton, Valery M.; Shih-Chieh Chen, Jay; Huang, Susan M.; Minassi, Alberto; Bisogno, Tiziana; Masuda, Kim; Tan, Bo; Roskoski, Robert; Cravatt, Benjamin F.; Di Marzo, Vincenzo; Walker, J. Michael (2009-10-01). "The biosynthesis of N-arachidonoyl dopamine (NADA), a putative endocannabinoid and endovanilloid, via conjugation of arachidonic acid with dopamine" . Prostaglandins, Leukotrienes and Essential Fatty Acids . 81 (4): 291–301. doi : 10.1016/j.plefa.2009.05.026 . ISSN 0952-3278 . PMC 2757501 . PMID 19570666 .
- ↑ Pajouhesh, H; Hancock, A J (1984-03-01). "Synthesis of cyclopentano-N-methylphosphatidylethanolamines: aminolysis during the use of methylamine" . Journal of Lipid Research . 25 (3): 310–312. doi : 10.1016/S0022-2275(20)37828-7 . ISSN 0022-2275 . PMID 6726084 . Retrieved 2017-12-15 .
External links
- General information about NADA.
Amino acid -derived |
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TRPA |
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TRPC |
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TRPM |
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TRPML |
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TRPP |
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TRPV |
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See also:
Receptor/signaling modulators
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Ion channel modulators
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