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) |
|---|---|
| Pages (from-to) | 983-991 |
| Number of pages | 9 |
| Journal | Neuropharmacology |
| Volume | 35 |
| Issue number | 7 |
| DOIs | |
| State | Published - 1996 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Anandamide, an endogenous cannabinoid, inhibits Shaker-related voltage-gated K+ channels
AU - Poling, J. S.
AU - Rogawski, Michael A
AU - Salem, N.
AU - Vicini, S.
PY - 1996
Y1 - 1996
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.
KW - Fatty acid
KW - N-acyl-ethanolamide
KW - Path clamp recording
KW - Recombinant potassium channel
UR - http://www.scopus.com/inward/record.url?scp=0013662082&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0013662082&partnerID=8YFLogxK
U2 - 10.1016/0028-3908(96)00130-X
DO - 10.1016/0028-3908(96)00130-X
M3 - Article
C2 - 8938728
AN - SCOPUS:0013662082
VL - 35
SP - 983
EP - 991
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
IS - 7
ER -