PMID: 8938728Jan 1, 1996Paper

Anandamide, an endogenous cannabinoid, inhibits Shaker-related voltage-gated K+ channels

Neuropharmacology
J S PolingS Vicini

Abstract

Anandamide has been identified in porcine brain as an endogenous cannabinoid receptor ligand and is believed to be a counterpart to the psychoactive component of marijuana, delta 9-tetrahydrocannabinol (delta 9-THC). Here we report that anandamide directly inhibits (IC50, 2.7 muM) Shaker-related Kv1.2 K+ channels that are found ubiquitously in the mammalian brain. Delta 9-THC also inhibited Kv1.2 channels with comparable potency (IC50, 2.4 muM), as did several N-acyl-ethanolamides with cannabinoid receptor binding activity. Potassium current inhibition occurred through a pertussis toxin-insensitive mechanism and was not prevented by the cannabinoid receptor antagonist SR141716A. Utilizing excised patches of Kv1.2 channel-rich membrane as a rapid and sensitive bioassay, we found that phospholipase D stimulated the release of an endogenous anandamide-like K+ channel blocker from rat brain slices. Structure-activity studies were consistent with the possibility that the released blocker was either anandamide or another N-acyl-ethanolamide.

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Citations

May 2, 2008·European Biophysics Journal : EBJ·Alison Gurney, Boris Manoury
Apr 6, 2004·Brain Research. Brain Research Reviews·John M McPartland
Feb 6, 2004·Pharmacology & Therapeutics·David E Nichols
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