Functional Role of High-Affinity Anandamide Transport, as Revealed by Selective Inhibition

• DOI: 10.1126/science.277.5329.1094
• Publication Date: 2002-07-27T09:52:08Z
• Authors: M. Beltramo; N. Stella; A. Calignano; S. Y. Lin; A. Makriyannis; D. Piomelli
• Keywords: Anandamide; GPR18

Anandamide, an endogenous ligand for central cannabinoid receptors, is released from neurons on depolarization and rapidly inactivated. Anandamide inactivation not completely understood, but it may occur by transport into cells or enzymatic hydrolysis. The compound N -(4-hydroxyphenyl)arachidonylamide (AM404) was shown to inhibit high-affinity anandamide accumulation in rat astrocytes vitro, indication that this resulted carrier-mediated transport. Although AM404 did activate receptors hydrolysis, enhanced receptor-mediated responses vitro vivo. data indicate be essential termination of the biological effects anandamide, represent a potential drug target.