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, Δ9-tetrahydrocannabinol (Δ9-THC). Here we report that anandamide directly inhibits (IC50, 2.7 μM) Shaker-related Kv1.2 K+ channels that are found ubiquitously in the mammalian brain. Δ9-THC also inhibited Kv1.2 channels with comparable potency (IC50, 2.4 μM), 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.
Original language | English (US) |
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Pages (from-to) | 983-991 |
Number of pages | 9 |
Journal | Neuropharmacology |
Volume | 35 |
Issue number | 7 |
DOIs | |
State | Published - 1996 |
Externally published | Yes |
Keywords
- Fatty acid
- N-acyl-ethanolamide
- Path clamp recording
- Recombinant potassium channel
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Drug Discovery
- Pharmacology