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

J. S. Poling, Michael A Rogawski, N. Salem, S. Vicini

Research output: Contribution to journalArticle

103 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)983-991
Number of pages9
JournalNeuropharmacology
Volume35
Issue number7
DOIs
StatePublished - 1996
Externally publishedYes

Fingerprint

Voltage-Gated Potassium Channels
Kv1.2 Potassium Channel
Cannabinoids
Cannabinoid Receptors
rimonabant
Dronabinol
Inhibitory Concentration 50
Brain
Cannabinoid Receptor Antagonists
Phospholipase D
Pertussis Toxin
Cannabis
Biological Assay
Potassium
Swine
Ligands
Membranes
anandamide

Keywords

  • Fatty acid
  • N-acyl-ethanolamide
  • Path clamp recording
  • Recombinant potassium channel

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Anandamide, an endogenous cannabinoid, inhibits Shaker-related voltage-gated K+ channels. / Poling, J. S.; Rogawski, Michael A; Salem, N.; Vicini, S.

In: Neuropharmacology, Vol. 35, No. 7, 1996, p. 983-991.

Research output: Contribution to journalArticle

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AU - Vicini, S.

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N2 - 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.

AB - 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.

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