187224-29-9Relevant articles and documents
Identification of endogenous acyl amino acids based on a targeted lipidomics approach
Tan, Bo,O'Dell, David K.,Yu, Y. William,Monn, M. Francesca,Hughes, H. Velocity,Burstein, Sumner,Walker, J. Michael
experimental part, p. 112 - 119 (2010/11/03)
Using a partially purified bovine brain extract, our lab identified three novel endogenous acyl amino acids in mammalian tissues. The presence of numerous amino acids in the body and their ability to form amides with several saturated and unsaturated fatty acids indicated the potential existence of a large number of heretofore unidentified acyl amino acids. Reports of several additional acyl amino acids that activate G-protein coupled receptors (e.g., N-arachidonoyl glycine, N- arachidonoyl serine) and transient receptor potential channels (e.g., N-arachidonoyl dopamine, N-acyl taurines) suggested that some or many novel acyl amino acids could serve as signaling molecules. Here, we used a targeted lipidomics approach including specific enrichment steps, nano-LC/MS/MS, high-throughput screening of the datasets with a potent search algorithm based on fragmention analysis, and quantification using the multiple reaction monitoring mode in Analyst software to measure the biological levels of acyl amino acids in rat brain. We successfully identified 50 novel endogenous acyl amino acids present at 0.2 to 69 pmol g-1 wet rat brain. Copyright
Potential neuroprotective drugs in cerebral ischemia: New saturated and polyunsaturated lipids coupled to hydrophilic moieties: Synthesis and biological activity
Biraboneye, Alain César,Madonna, Sébastien,Laras, Younes,Krantic, Slavica,Maher, Pamela,Kraus, Jean-Louis
experimental part, p. 4358 - 4369 (2010/02/17)
The ganglioside GM1 has neuroprotective effects but is not of therapeutic value because of its lack of bioavailability. Thus, molecules that mimic GM1 represent a novel approach to neuroprotection. We have synthesized 19 small GM1-like analogues whose simplified structure includes a hydrophobic saturated or unsaturated moiety linked to a hydrophilic moiety. We report their neuroprotective effects in two distinct models of nerve cell death using hippocampus-derived HT22 cells. We found that several analogues protected the HT22 cells from death at concentrations ranging from 2 to 5 μM. Additional neuroprotective assays using cortical slices injured by glutamate confirmed these results. Since members of the MAP kinase family are known to be key players in nerve cell survival and death, we characterized the role of these kinases in the neuroprotective mechanisms of the GM1-like analogues. Interestingly, the results indicate that the compounds provide neuroprotection through distinct mechanisms of action.
Structural requirements for binding of anandamide-type compounds to the brain cannabinoid receptor
Sheskin, Tzviel,Hanu?, Lumir,Slager, Joram,Vogel, Zvi,Mechoulam, Raphael
, p. 659 - 667 (2007/10/03)
In order to establish the structural requirements for binding to the brain cannabinoid receptor (CB1), we have synthesized numerous fatty acid amides, ethanolamides, and some related simple derivatives and have determined their K(i) values. A f
Mead ethanolamide, a novel eicosanoid, is an agonist for the central (CB1) and peripheral (CB2) cannabinoid receptors
Priller, Josef,Briley, Eileen M.,Mansouri, Jaleh,Devane, William A.,Mackie, Ken,Felder, Christian C.
, p. 288 - 292 (2007/10/03)
The recently discovered endogenous agonist for the cannabinoid receptor, anandamide (arachidonylethanolamide), can be formed enzymatically by the condensation of arachidonic acid with ethanolamine. 5Z,8Z,11Z-Eicosatrienoic acid (mead acid) has been found to substitute for arachidonic acid in the sn- 2 position of phospholipids and accumulate during periods of dietary fatty acid deprivation in rats. In the present study, the chemically synthesized ethanolamide of mead acid was evaluated as a potential agonist at the two known subtypes of cannabinoid receptor: CB1 (central) and CB2 (peripheral). This compound was equipotent to anandamide in competing with [3H]CP55,940 binding to plasma membranes prepared from L cells expressing the human CB1 receptor and from ATt-20 cells expressing the human CB2 receptor. Mead ethanolamide was also equipotent to anandamide in inhibiting forskolin- stimulated cAMP accumulation in cells expressing the CB1 receptor. It inhibited N-type calcium currents with a lower potency than anandamide. Mead and arachidonic acid were equally efficacious as substrates for the enzymatic synthesis of their respective ethanolamides in rat and adult human hippocampal P2 membranes. Palmitic acid was not an effective substrate for the enzymatic synthesis of palmitoyl ethanolamide. Mead ethanolamide exhibits several characteristics of a novel agonist to CB1 and CB2 receptors and may represent another candidate endogenous ligand for the CB1 receptor. Due to the anticonvulsant properties of GABA and the positional similarity of L- serine to ethanolamine in membrane phospholipids, these compounds were synthetically coupled to arachidonic acid, and their resulting arachidonamides were tested as potential cannabinoid agonists. The arachidonamides of GABA and L-serine were inactive in both binding and functional assays at the CB1 receptor.
