Publication Date:
1997-08-22
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beltramo, M -- Stella, N -- Calignano, A -- Lin, S Y -- Makriyannis, A -- Piomelli, D -- New York, N.Y. -- Science. 1997 Aug 22;277(5329):1094-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Neurosciences Institute, 10640 J. J. Hopkins Drive, San Diego, CA 92121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9262477" target="_blank"〉PubMed〈/a〉
Keywords:
Analgesics/pharmacology
;
Animals
;
Arachidonic Acids/antagonists & inhibitors/*metabolism/pharmacology
;
Astrocytes/drug effects/*metabolism
;
Benzoxazines
;
Biological Transport/drug effects
;
Bromcresol Green/pharmacology
;
Cannabinoids/antagonists & inhibitors/*metabolism/pharmacology
;
Cells, Cultured
;
Colforsin/pharmacology
;
Cyclic AMP/metabolism
;
Endocannabinoids
;
Male
;
Mice
;
Morpholines/pharmacology
;
Naphthalenes/pharmacology
;
Neurons/drug effects/*metabolism
;
Piperidines/pharmacology
;
Polyunsaturated Alkamides
;
Pyrazoles/pharmacology
;
Rats
;
Receptors, Cannabinoid
;
Receptors, Drug/agonists/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
