Acyl ethanolamides

Bisogno T, Ventriglia M, Milone A, Mosca M, Cimino G, Di Marzo V (1997) Occurrence and metabolism of anandamide and related acyl-ethanolamides in ovaries of the sea urchin Paracentrotus lividus. Biochim Biophys Acta 1345 338-348... 

Inhibitory Effects of Acyl Ethanolamides and Cannabinoids on Sperm Fertilizing Capacity and Egg-Jelly-Stimulated Acrosome Reactions in Sea Urchins... 

As an example of the application of metabolomics, we will refer to the substrates of the enzyme fatty acyl amide hydrolase (FAAH) that regulates several brain lipids that have interesting pharmacological properties including effects on the control of pain. It is well known that some fatty acyl amides of ethanolamine are substrates of FAAH, such as the ethanolamide of arachidonic acid (anandamide), which is an endogenous ligand of cannabinoid receptors. 

Burstein and Hunter (1995) observed that THC stimulated the biosynthesis of anandamide in neuroblastoma cells employing either ethanolamine or arachidonic acid as the label. Anandamide bios5mthesis has also been shown to occur in primary cultures of rat brain neurons labelled with [H]-ethanolamine when stimulated with ionomycin, a Ca ionophore (Di Marzo et al. 1994). These authors proposed an alternate model for the biosynthesis of anandamide in which N-arachidonoyl phosphatidyl ethanolamine is cleaved by a phospholipase D activity to yield phosphatidic acid and ararchidonoylethanolamide. This model is based upon extensive studies undertaken by Schmid and collaborators (1990), who have shown that fatty acid ethanolamide formation results from the N-acylation of phosphatidyl ethanolamine by a transacylase to form N-acyl phosphatidylethanolamine. Possibly resulting from postmortem changes, this compound is subsequently hydrolyzed to the fatty acid ethanolamide and the corresponding phosphatide by a phosphodiesterase, phospholipase D. 

Endocannabinoid SAR indicates that the CBi receptor recognizes ethanolamides whose fatty acid acyl chains have 20 or 22 carbons, with at least three homoallylic... 

Acyl Chain SAR Fatty Acid Ethanolamides Effect of Unsaturation... 

The degree of unsaturation is not the only acyl chain requirement for reeogtrition at the CB, reeeptor. Sheskin and eo-workers (1997) found that in an n-3 series, highly unsaturated analogs had poor to no CBi affinity as revealed by the following series of n-3 ethanolamide derivatives 20 5, ... 

The mammalian endocannabinoid family inclndes fonr lipid Af-fatty acyl-ethanolamines (NAEs), two Af-acyl-dopamines, a lipid ester, and a lipid ether. The NAEs are Af-arachidonoyl ethanolamine (anan-damide, AEA) (Devane et al., 1992), docosatetraenoyl-ethanolamide and di-homo-y-hnolenoyl-ethanolamide (Hanus et al., 1993), and O-arachidonoyl ethanolamide (virodhamine) (Porter et al., 2002). The Af-acyl-dopamines are Af-arachidonoyl-dopamine (NADA) and Af-oleoyl-dopamine (Hnang et al., 2002). The lipid ester is sn-2 arachidonoyl glycerol (2-AG) (Mechonlam et al., 1995 Sugiura et al., 1995). The lipid ether is sn-2 arachidonoyl glyceryl ether (noladin ether) (Hanus et al., 2001). 

Acyl chlorides 176 and 177 have been reduced to primary alcohols containing two tritium equivalents, as with intermediates in the preparation of the glutamate-gated chloride channel modulator nodulisporic [ H]ethanolamide (22Ci/mmol, 1771 and the NADHiubiquinone oxidoreductase photoaffinitv probe 179 (4.7 Ci/mmol), respectively. 

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