Faculty Collaboration Database

Arachidonylethanolamide (anandamide) binds with low affinity to dihydropyridine binding sites in brain membranes. Prostaglandins Leukot Essent Fatty Acids 1997 Dec;57(6):551-4

Date

02/07/1998

Pubmed ID

9431821

DOI

10.1016/s0952-3278(97)90559-7

Scopus ID

2-s2.0-0030827460 (requires institutional sign-in at Scopus site)   24 Citations

Abstract

The purpose of this study was to explore the hypothesis that the dihydropyridine (DHP) binding site of the L-type calcium channel is a high affinity binding site for the cannabimimetic arachidonylethanolamide (AEA). Binding affinities were determined from competition isotherms using the DHP analog [3H]PN-200. AEA competed for [3H]PN-200 binding with a K(I) of 40 +/- 4 microM. Inclusion of phenylmethylsulfonyl fluoride to inhibit an amidohydrolase that converts AEA to arachidonic acid had little effect on the K(I) of AEA (48 +/- 6 microM). Arachidonic acid had a slightly higher K(I) (120 +/- 11 microM) and other N-acylethanolamides examined (linolenylethanolamide, dihomo-gamma-linolenylethanolamide, docosatetraenylethanolamide, and palmitoylethanolamide) had no effect on [3H]PN-200 binding at concentrations as high as 10 microM. Our conclusions are that AEA binds to the DHP binding site with relatively low affinity and its conversion to arachidonic acid is not required for binding.

Author List

Jarrahian A, Hillard CJ

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amides
Amidohydrolases
Animals
Arachidonic Acids
Binding Sites
Binding, Competitive
Brain
Cell Membrane
Dihydropyridines
Endocannabinoids
Ethanolamines
Male
Polyunsaturated Alkamides
Rats
Rats, Sprague-Dawley
Tosyl Compounds