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

Neuropharmacology. 1996;35(7):983-91. doi: 10.1016/0028-3908(96)00130-x.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arachidonic Acids / pharmacology*
  • Brain / drug effects
  • Brain / metabolism
  • Cells, Cultured
  • Dronabinol / pharmacology
  • Endocannabinoids
  • Kv1.2 Potassium Channel
  • Patch-Clamp Techniques
  • Phospholipase D / pharmacology
  • Piperidines / pharmacology
  • Polyunsaturated Alkamides
  • Potassium Channel Blockers*
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Pyrazoles / pharmacology
  • Rats
  • Receptors, Cannabinoid
  • Receptors, Drug / antagonists & inhibitors
  • Rimonabant
  • Shaker Superfamily of Potassium Channels
  • Structure-Activity Relationship
  • Transfection

Substances

  • Arachidonic Acids
  • Endocannabinoids
  • Kcna2 protein, rat
  • Kv1.2 Potassium Channel
  • Piperidines
  • Polyunsaturated Alkamides
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Shaker Superfamily of Potassium Channels
  • Dronabinol
  • Phospholipase D
  • Rimonabant
  • anandamide