Abstract
The effects of cannabidiol (CBD), a non-psychoactive ingredient of cannabis plant, on the function of the cloned α7 subunit of the human nicotinic acetylcholine (α7 nACh) receptor expressed in Xenopus oocytes were tested using the two-electrode voltage-clamp technique. CBD reversibly inhibited ACh (100 μM)-induced currents with an IC50 value of 11.3 μM. Other phytocannabinoids such as cannabinol and Δ9-tetrahydrocannabinol did not affect ACh-induced currents. CBD inhibition was not altered by pertussis toxin treatment. In addition, CBD did not change GTP-γ-S binding to the membranes of oocytes injected with α7 nACh receptor cRNA. The effect of CBD was not dependent on the membrane potential. CBD (10 μM) did not affect the activity of endogenous Ca2+-dependent Cl- channels, since the extent of inhibition by CBD was unaltered by intracellular injection of the Ca 2+ chelator BAPTA and perfusion with Ca2+-free bathing solution containing 2 mM Ba2+. Inhibition by CBD was not reversed by increasing ACh concentrations. Furthermore, specific binding of [ 125I] α-bungarotoxin was not inhibited by CBD (10 μM) in oocytes membranes. Using whole cell patch clamp technique in CA1 stratum radiatum interneurons of rat hippocampal slices, currents induced by choline, a selective-agonist of α7-receptor induced currents were also recoded. Bath application of CBD (10 μM) for 10 min caused a significant inhibition of choline induced currents. Finally, in hippocampal slices, [ 3H] norepinephrine release evoked by nicotine (30 μM) was also inhibited by 10 μM CBD. Our results indicate that CBD inhibits the function of the α7-nACh receptor.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 310-319 |
| Number of pages | 10 |
| Journal | European Journal of Pharmacology |
| Volume | 720 |
| Issue number | 1-3 |
| DOIs | |
| State | Published - Nov 15 2013 |
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Keywords
- Cannabidiol
- Cannabinoids
- Nicotinic receptors
- Xenopus oocyte
ASJC Scopus subject areas
- Pharmacology
Cite this
Effects of cannabidiol on the function of α7-nicotinic acetylcholine receptors. / Mahgoub, Mohamed; Keun-Hang, Susan Yang; Sydorenko, Vadym; Ashoor, Abrar; Kabbani, Nadine; Al Kury, Lina; Sadek, Bassem; Howarth, Christopher F.; Isaev, Dmytro; Galadari, Sehamuddin; Oz, Murat.
In: European Journal of Pharmacology, Vol. 720, No. 1-3, 15.11.2013, p. 310-319.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of cannabidiol on the function of α7-nicotinic acetylcholine receptors
AU - Mahgoub, Mohamed
AU - Keun-Hang, Susan Yang
AU - Sydorenko, Vadym
AU - Ashoor, Abrar
AU - Kabbani, Nadine
AU - Al Kury, Lina
AU - Sadek, Bassem
AU - Howarth, Christopher F.
AU - Isaev, Dmytro
AU - Galadari, Sehamuddin
AU - Oz, Murat
PY - 2013/11/15
Y1 - 2013/11/15
N2 - The effects of cannabidiol (CBD), a non-psychoactive ingredient of cannabis plant, on the function of the cloned α7 subunit of the human nicotinic acetylcholine (α7 nACh) receptor expressed in Xenopus oocytes were tested using the two-electrode voltage-clamp technique. CBD reversibly inhibited ACh (100 μM)-induced currents with an IC50 value of 11.3 μM. Other phytocannabinoids such as cannabinol and Δ9-tetrahydrocannabinol did not affect ACh-induced currents. CBD inhibition was not altered by pertussis toxin treatment. In addition, CBD did not change GTP-γ-S binding to the membranes of oocytes injected with α7 nACh receptor cRNA. The effect of CBD was not dependent on the membrane potential. CBD (10 μM) did not affect the activity of endogenous Ca2+-dependent Cl- channels, since the extent of inhibition by CBD was unaltered by intracellular injection of the Ca 2+ chelator BAPTA and perfusion with Ca2+-free bathing solution containing 2 mM Ba2+. Inhibition by CBD was not reversed by increasing ACh concentrations. Furthermore, specific binding of [ 125I] α-bungarotoxin was not inhibited by CBD (10 μM) in oocytes membranes. Using whole cell patch clamp technique in CA1 stratum radiatum interneurons of rat hippocampal slices, currents induced by choline, a selective-agonist of α7-receptor induced currents were also recoded. Bath application of CBD (10 μM) for 10 min caused a significant inhibition of choline induced currents. Finally, in hippocampal slices, [ 3H] norepinephrine release evoked by nicotine (30 μM) was also inhibited by 10 μM CBD. Our results indicate that CBD inhibits the function of the α7-nACh receptor.
AB - The effects of cannabidiol (CBD), a non-psychoactive ingredient of cannabis plant, on the function of the cloned α7 subunit of the human nicotinic acetylcholine (α7 nACh) receptor expressed in Xenopus oocytes were tested using the two-electrode voltage-clamp technique. CBD reversibly inhibited ACh (100 μM)-induced currents with an IC50 value of 11.3 μM. Other phytocannabinoids such as cannabinol and Δ9-tetrahydrocannabinol did not affect ACh-induced currents. CBD inhibition was not altered by pertussis toxin treatment. In addition, CBD did not change GTP-γ-S binding to the membranes of oocytes injected with α7 nACh receptor cRNA. The effect of CBD was not dependent on the membrane potential. CBD (10 μM) did not affect the activity of endogenous Ca2+-dependent Cl- channels, since the extent of inhibition by CBD was unaltered by intracellular injection of the Ca 2+ chelator BAPTA and perfusion with Ca2+-free bathing solution containing 2 mM Ba2+. Inhibition by CBD was not reversed by increasing ACh concentrations. Furthermore, specific binding of [ 125I] α-bungarotoxin was not inhibited by CBD (10 μM) in oocytes membranes. Using whole cell patch clamp technique in CA1 stratum radiatum interneurons of rat hippocampal slices, currents induced by choline, a selective-agonist of α7-receptor induced currents were also recoded. Bath application of CBD (10 μM) for 10 min caused a significant inhibition of choline induced currents. Finally, in hippocampal slices, [ 3H] norepinephrine release evoked by nicotine (30 μM) was also inhibited by 10 μM CBD. Our results indicate that CBD inhibits the function of the α7-nACh receptor.
KW - Cannabidiol
KW - Cannabinoids
KW - Nicotinic receptors
KW - Xenopus oocyte
UR - http://www.scopus.com/inward/record.url?scp=84890129248&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84890129248&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2013.10.011
DO - 10.1016/j.ejphar.2013.10.011
M3 - Article
C2 - 24140434
AN - SCOPUS:84890129248
VL - 720
SP - 310
EP - 319
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -