N-arachidonylethanolamide-induced increase in aqueous humor outflow facility.
OBJECTIVE
To study the effects of N-arachidonylethanolamide (anandamide [AEA]) on aqueous humor outflow and to investigate the existence and activity of fatty acid amide hydrolase (FAAH), an AEA metabolic enzyme in trabecular meshwork (TM) tissue.


METHODS
The effects of AEA on aqueous humor outflow were measured using a porcine anterior segment-perfused organ culture model. Western blot analysis was used to study the expression of FAAH, and a thin-layer chromatography-based approach was used to measure the enzymatic activity of FAAH in TM tissue.


RESULTS
Administration of AEA caused a transient enhancement of aqueous humor outflow facility. In the presence of 100 nM URB597, an FAAH inhibitor, the effect of 10 nM AEA on outflow facility was prolonged by at least 4 hours. The AEA-induced enhancement of outflow facility was blocked by SR141716A, a CB1 antagonist, and was partially blocked by SR144528, a CB2 antagonist. In Western blot studies, positive signals were detected on TM tissues with an anti-FAAH antibody. In the enzyme activity studies, the enzymatic activity of AEA hydrolysis was detected in TM tissues, and this activity was reduced with the addition of 100 nM URB597.


CONCLUSIONS
Results from this study demonstrate that the administration of AEA increases aqueous humor outflow facility and that this effect of AEA involves CB1 and CB2 cannabinoid receptors. In addition, this study reveals the existence and the activity of FAAH, an AEA-metabolizing enzyme, in the TM tissues.
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA.
Ya Fatou
YF
Njie
Zhuanhong
Z
Qiao
Zhen
Z
Xiao
Wei
W
Wang
Zhao-Hui
ZH
Song
D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects / Q000378:metabolism; D001082:Aqueous Humor / Q000378:metabolism*; D001095:Arachidonic Acids / Q000008:administration & dosage*; D001549:Benzamides / Q000494:pharmacology; D015153:Blotting, Western; D001892:Camphanes / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators / Q000008:administration & dosage*; D002219:Carbamates / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D063388:Endocannabinoids; D009924:Organ Culture Techniques; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage*; D011720:Pyrazoles / Q000494:pharmacology; D043882:Receptors, Cannabinoid / Q000378:metabolism; D000077285:Rimonabant; D013552:Swine; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D001549:Benzamides; D001892:Camphanes; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators; D002219:Carbamates; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D000077285:Rimonabant; D000099252:Fatty Acid Amide Hydrolases; C110630:SR 144528; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C078814:anandamide