Disease relevance of AEA

• Cannabinoids, including the endogenous ligand anandamide (arachidonyl ethanolamide), elicit pronounced hypotension in rats via activation of peripherally located CB1 cannabinoid receptors, which have been also implicated in endotoxin (lipopolysaccharide [LPS])-induced hypotension [1].

High impact information on AEA

• Arachidonoyl ethanolamide (anandamide) is a naturally occurring brain constituent that binds to a specific brain cannabinoid receptor (CBR1) [2].
• Inhibitors of arachidonoyl ethanolamide hydrolysis [2].
• Although the N-arachidonoyl ethanolamine (anandamide) binds to cannabinoid receptors and has been implicated in the suppression of pain, its rapid catabolism in vivo by fatty acid amide hydrolase (FAAH) has presented a challenge in investigating the physiological functions of this endogenous cannabinoid [3].
• 4. In contrast to RTX, PPAHV and capsaicin, the putative endogenous vanilloid receptor agonist, arachidonyl ethanolamide (AEA), and non-pungent capsaicin derivative, olvanil, had no direct effect on respiration [4].
• Human mast cells (HMC-1) take up anandamide (arachidonoyl-ethanolamide, AEA) with a saturable process (K(m)=200+/-20 nM, V(max)=25+/-3 pmol min(-1) mg protein(-1)), enhanced two-fold over control by nitric oxide-donors [5].

Biological context of AEA

• The endogenous cannabinoid anandamide (arachidonyl ethanolamide, 4 mg/kg i.v.) decreased blood pressure by 40+/-7 mm Hg by reducing systemic vascular resistance index from 3.3+/-0.1 to 2.3+/-0.1 mm Hg min/ml/100 g (P<0.05), leaving cardiac index and stroke volume index unchanged [6].
• Arachidonyl ethanolamide induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1 [7].
• The present study attempts to indirectly determine if a neuronal cannabinoid (CB1) receptor mediates the intraocular pressure (IOP) reduction effects of arachidonoyl ethanolamide (AEA), its R-alpha-isopropyl analog, and the non-classical cannabinoid, CP-55,940 [8].

Anatomical context of AEA

• In the present study, we analyzed the effect of arachidonyl ethanolamide (AEA) on cervical carcinoma (CxCa) cell lines [7].
• Isolated human atrial heart muscle preparations were stimulated by electrical field with 1 Hz to contract isometrically at optimal length and were challenged with the endogenous cannabinoid arachidonyl ethanolamide (anandamide), the metabolically stable analogue R-methanandamide, and the potent synthetic CB(1) receptor agonist HU-210 [9].

Associations of AEA with other chemical compounds

• We describe a simple fluorescence displacement assay to measure hydrolysis of arachidonoyl ethanolamide and oleoyl amide, two important pharmacological compounds [10].
• Anandamide (arachidonoyl-ethanolamide, AnNH) and 2-arachidonoyl-glycerol (2-AG) have been suggested to act as endogenous agonists at the brain cannabinoid receptor, and their biosynthetic and degradative mechanisms in nervous tissues and cells have also been partially elucidated [11].
• Fatty acid amide hydrolase (FAAH) catalyzes the hydrolysis of bioactive fatty acid amides and esters such as the endogenous cannabinoid receptor ligands, anandamide (N-arachidonoyl-ethanolamine) and 2-arachidonoylglycerol, and the putative sleep inducing factor cis-9-octadecenoamide (oleamide) [12].
• Altogether, these data demonstrate that the physiological effects of anandamide on endothelial cells depend on the status of integrin clustering [13].

Gene context of AEA

• The N-acylphosphatidylethanolamine-hydrolysing phospholipase D (NAPE-PLD) generates N-acylethanolamines, including N-arachidonoyl-ethanolamine (anandamide), that may be neuroprotective and analgesic [14].
• Arachidonoyl ethanolamide (anandamide) is an endogenous ligand for cannabinoid receptors (CB1, CB2) and a putative neurotransmitter [15].
• NAGly is a potent inhibitor of the fatty acid amide hydrolase (FAAH), the enzyme primarily responsible for the degradation of the endocannabinoid N-arachidonoyl-ethanolamine (anandamide), and was shown recently to elevate the blood levels of the this analgesic compound [16].
• Together, these data provide evidence for a multistep pathway for the production of anandamide in the nervous system by the sequential actions of Abh4 and GDE1 [17].

References