TY - JOUR
T1 - Elevated circulating levels of anandamide after administration of the transport inhibitor, AM404
AU - Giuffrida, Andrea
AU - Rodriguez De Fonseca, Fernando
AU - Nava, Felice
AU - Loubet-Lescoulié, Patrick
AU - Piomelli, Daniele
N1 - Funding Information:
We thank S. Chen and S.K. Kathuria for their excellent technical help. The financial support of NIDA under Grant number DA12413 and DA12653 (to D.P.) is gratefully acknowledged. Additional support was provided by the National Alliance for Research on Schizophrenia and Depression.
PY - 2000/11/17
Y1 - 2000/11/17
N2 - The biological actions of the endogenous cannabinoid anandamide are terminated by carrier-mediated transport into neurons and astrocytes, followed by enzymatic hydrolysis. Anandamide transport is inhibited by the compound N-(4-hydroxyphenyl)arachidonylamide (AM404). AM404 potentiates several responses elicited by administration of exogenous anandamide, suggesting that it may also protect endogenous anandamide from inactivation. To test this hypothesis, we studied the effects of AM404 on the plasma levels of anandamide using high-performance liquid chromatography/mass spectrometry (HPLC/MS). Systemic administration of AM404 (10 mg kg-1 intraperitoneal, i.p.) caused a gradual increase of anandamide in rat plasma, which was significantly different from untreated controls at 60 and 120 min after drug injection. In plasma, both AM404 and anandamide were associated with a plasma protein, which we identified as albumin by non-denaturing polyacrylamide gel electrophoresis. AM404 (10 mg kg-1, i.p.) caused a time-dependent decrease of motor activity, which was reversed by the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide·hydrochloride (SR141716A, 0.5 mg kg-1, i.p). These results are consistent with the hypothesis that AM404 inhibits anandamide inactivation in vivo. (C) 2000 Elsevier Science B.V.
AB - The biological actions of the endogenous cannabinoid anandamide are terminated by carrier-mediated transport into neurons and astrocytes, followed by enzymatic hydrolysis. Anandamide transport is inhibited by the compound N-(4-hydroxyphenyl)arachidonylamide (AM404). AM404 potentiates several responses elicited by administration of exogenous anandamide, suggesting that it may also protect endogenous anandamide from inactivation. To test this hypothesis, we studied the effects of AM404 on the plasma levels of anandamide using high-performance liquid chromatography/mass spectrometry (HPLC/MS). Systemic administration of AM404 (10 mg kg-1 intraperitoneal, i.p.) caused a gradual increase of anandamide in rat plasma, which was significantly different from untreated controls at 60 and 120 min after drug injection. In plasma, both AM404 and anandamide were associated with a plasma protein, which we identified as albumin by non-denaturing polyacrylamide gel electrophoresis. AM404 (10 mg kg-1, i.p.) caused a time-dependent decrease of motor activity, which was reversed by the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide·hydrochloride (SR141716A, 0.5 mg kg-1, i.p). These results are consistent with the hypothesis that AM404 inhibits anandamide inactivation in vivo. (C) 2000 Elsevier Science B.V.
KW - Anandamide
KW - Anandamide transport
KW - Cannabinoid
KW - Fatty acid ethanolamides
KW - High-performance liquid chromatography
KW - Mass spectrometry
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U2 - 10.1016/S0014-2999(00)00786-X
DO - 10.1016/S0014-2999(00)00786-X
M3 - Article
C2 - 11080522
AN - SCOPUS:0034680851
SN - 0014-2999
VL - 408
SP - 161
EP - 168
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2
ER -