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Anandamide transport inhibitor AM404 and structurally related compounds inhibit synaptic transmission between rat hippocampal neurons in culture independent of cannabinoid CB1 receptors.
Eur J Pharmacol 2004; 496(1-3):33-9EJ

Abstract

N-(hydroxyphenyl)-arachidonamide (AM404) is an inhibitor of endocannabinoid transport. We examined the effects of AM404 on glutamatergic synaptic transmission using network-driven increases in intracellular Ca2+ concentration ([Ca2+] spikes) as an assay. At a concentration of 1 microM AM404 inhibited [Ca2+]i spiking by 73+/-8%. The cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A), the vanilloid VR1 receptor antagonist capsazepine (CPZ), and treatment with pertussis toxin failed to block AM404-mediated inhibition. AM404 (3 microM) inhibited action-potential-evoked Ca2+ influx by 58+/-3% but failed to affect calcium influx evoked by depolarization with 30 mM K+, suggesting that the inhibition of electrically evoked [Ca2+]i increases and that [Ca2+]i spiking was due to inhibition of Na+ channels. Palmitoylethanolamide (PMEA), capsaicin (CAP) and (5Z,8Z,11Z,14Z)-N-(4-hydroxy-2-methylphenyl)-5,8,11,14-eicosatetraenamide (VDM11), compounds structurally similar to AM404, inhibited [Ca2+]i spiking by 34+/-10%, 42+/-18% and 67+/-12%, respectively. Thus, AM404 and related compounds inhibit depolarization-induced Ca2+ influx independent of cannabinoid receptors, suggesting caution when using these agents as pharmacological probes to study synaptic transmission.

Authors+Show Affiliations

Department of Pharmacology University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church Street, Minneapolis, MN 55455, USA.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15288572

Citation

Kelley, Brooke G., and Stanley A. Thayer. "Anandamide Transport Inhibitor AM404 and Structurally Related Compounds Inhibit Synaptic Transmission Between Rat Hippocampal Neurons in Culture Independent of Cannabinoid CB1 Receptors." European Journal of Pharmacology, vol. 496, no. 1-3, 2004, pp. 33-9.
Kelley BG, Thayer SA. Anandamide transport inhibitor AM404 and structurally related compounds inhibit synaptic transmission between rat hippocampal neurons in culture independent of cannabinoid CB1 receptors. Eur J Pharmacol. 2004;496(1-3):33-9.
Kelley, B. G., & Thayer, S. A. (2004). Anandamide transport inhibitor AM404 and structurally related compounds inhibit synaptic transmission between rat hippocampal neurons in culture independent of cannabinoid CB1 receptors. European Journal of Pharmacology, 496(1-3), pp. 33-9.
Kelley BG, Thayer SA. Anandamide Transport Inhibitor AM404 and Structurally Related Compounds Inhibit Synaptic Transmission Between Rat Hippocampal Neurons in Culture Independent of Cannabinoid CB1 Receptors. Eur J Pharmacol. 2004 Aug 2;496(1-3):33-9. PubMed PMID: 15288572.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anandamide transport inhibitor AM404 and structurally related compounds inhibit synaptic transmission between rat hippocampal neurons in culture independent of cannabinoid CB1 receptors. AU - Kelley,Brooke G, AU - Thayer,Stanley A, PY - 2003/12/04/received PY - 2004/06/03/revised PY - 2004/06/08/accepted PY - 2004/8/4/pubmed PY - 2005/1/29/medline PY - 2004/8/4/entrez SP - 33 EP - 9 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 496 IS - 1-3 N2 - N-(hydroxyphenyl)-arachidonamide (AM404) is an inhibitor of endocannabinoid transport. We examined the effects of AM404 on glutamatergic synaptic transmission using network-driven increases in intracellular Ca2+ concentration ([Ca2+] spikes) as an assay. At a concentration of 1 microM AM404 inhibited [Ca2+]i spiking by 73+/-8%. The cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A), the vanilloid VR1 receptor antagonist capsazepine (CPZ), and treatment with pertussis toxin failed to block AM404-mediated inhibition. AM404 (3 microM) inhibited action-potential-evoked Ca2+ influx by 58+/-3% but failed to affect calcium influx evoked by depolarization with 30 mM K+, suggesting that the inhibition of electrically evoked [Ca2+]i increases and that [Ca2+]i spiking was due to inhibition of Na+ channels. Palmitoylethanolamide (PMEA), capsaicin (CAP) and (5Z,8Z,11Z,14Z)-N-(4-hydroxy-2-methylphenyl)-5,8,11,14-eicosatetraenamide (VDM11), compounds structurally similar to AM404, inhibited [Ca2+]i spiking by 34+/-10%, 42+/-18% and 67+/-12%, respectively. Thus, AM404 and related compounds inhibit depolarization-induced Ca2+ influx independent of cannabinoid receptors, suggesting caution when using these agents as pharmacological probes to study synaptic transmission. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/15288572/Anandamide_transport_inhibitor_AM404_and_structurally_related_compounds_inhibit_synaptic_transmission_between_rat_hippocampal_neurons_in_culture_independent_of_cannabinoid_CB1_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014299904006120 DB - PRIME DP - Unbound Medicine ER -