학술논문

Functional Role of High-Affinity Anandamide Transport, as Revealed by Selective Inhibition
Document Type
article
Source
Science. 277(5329)
Subject
Neurosciences
Substance Misuse
Drug Abuse (NIDA only)
Analgesics
Animals
Arachidonic Acids
Astrocytes
Benzoxazines
Biological Transport
Bromcresol Green
Cannabinoids
Cells
Cultured
Colforsin
Cyclic AMP
Endocannabinoids
Male
Mice
Morpholines
Naphthalenes
Neurons
Piperidines
Polyunsaturated Alkamides
Pyrazoles
Rats
Receptors
Cannabinoid
Receptors
Drug
Rimonabant
General Science & Technology
Language
Abstract
Anandamide, an endogenous ligand for central cannabinoid receptors, is released from neurons on depolarization and rapidly inactivated. Anandamide inactivation is not completely understood, but it may occur by transport into cells or by enzymatic hydrolysis. The compound N-(4-hydroxyphenyl)arachidonylamide (AM404) was shown to inhibit high-affinity anandamide accumulation in rat neurons and astrocytes in vitro, an indication that this accumulation resulted from carrier-mediated transport. Although AM404 did not activate cannabinoid receptors or inhibit anandamide hydrolysis, it enhanced receptor-mediated anandamide responses in vitro and in vivo. The data indicate that carrier-mediated transport may be essential for termination of the biological effects of anandamide, and may represent a potential drug target.