Abstract
1. Human α7 nicotinic acetylcholine (ACh) receptors were expressed in Xenopus oocytes and the effects of the N-methyl-D-aspartate (NMDA) receptor open channel blockers memantine and cerestat on this receptor were examined using two-electrode voltage-clamp recordings and 125I-α- bungarotoxin (125I-α-bgtx) binding. 2. Memantine and cerestat produced complete inhibition of ACh-induced inward currents with affinities similar to that reported for native NMDA receptors. Cerestat, IC 50 1.7 (-1; +2) μM, was more potent than memantine, IC 50 5 (-3; +8) μM, and the effects of both drugs were fully and rapidly reversible. 3. Inhibition of α7 receptor function was voltage-independent, and it occurred at concentrations far lower than those needed to inhibit (never completely) binding of 125I-α-bgtx to α7 receptors, suggesting that the effects of memantine or cerestat are noncompetitive. 4. These results provide evidence that human α7 receptors are inhibited by memantine and cerestat and suggest that caution should be applied when using these compounds to study systems in which NMDA and nACh receptors co-exist.
| Original language | English |
|---|---|
| Pages (from-to) | 1313-1319 |
| Number of pages | 7 |
| Journal | British Journal of Pharmacology |
| Volume | 140 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Dec 2003 |
| Externally published | Yes |
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Inhibition of human α7 nicotinic acetylcholine receptors by open channel blockers of N-methyl-D-aspartate receptors. / Maskell, Peter D.; Speder, Pauline; Newberry, Nigel R.; Bermudez, Isabel.
In: British Journal of Pharmacology, Vol. 140, No. 7, 12.2003, p. 1313-1319.Research output: Contribution to journal › Article
TY - JOUR
T1 - Inhibition of human α7 nicotinic acetylcholine receptors by open channel blockers of N-methyl-D-aspartate receptors
AU - Maskell, Peter D.
AU - Speder, Pauline
AU - Newberry, Nigel R.
AU - Bermudez, Isabel
PY - 2003/12
Y1 - 2003/12
N2 - 1. Human α7 nicotinic acetylcholine (ACh) receptors were expressed in Xenopus oocytes and the effects of the N-methyl-D-aspartate (NMDA) receptor open channel blockers memantine and cerestat on this receptor were examined using two-electrode voltage-clamp recordings and 125I-α- bungarotoxin (125I-α-bgtx) binding. 2. Memantine and cerestat produced complete inhibition of ACh-induced inward currents with affinities similar to that reported for native NMDA receptors. Cerestat, IC 50 1.7 (-1; +2) μM, was more potent than memantine, IC 50 5 (-3; +8) μM, and the effects of both drugs were fully and rapidly reversible. 3. Inhibition of α7 receptor function was voltage-independent, and it occurred at concentrations far lower than those needed to inhibit (never completely) binding of 125I-α-bgtx to α7 receptors, suggesting that the effects of memantine or cerestat are noncompetitive. 4. These results provide evidence that human α7 receptors are inhibited by memantine and cerestat and suggest that caution should be applied when using these compounds to study systems in which NMDA and nACh receptors co-exist.
AB - 1. Human α7 nicotinic acetylcholine (ACh) receptors were expressed in Xenopus oocytes and the effects of the N-methyl-D-aspartate (NMDA) receptor open channel blockers memantine and cerestat on this receptor were examined using two-electrode voltage-clamp recordings and 125I-α- bungarotoxin (125I-α-bgtx) binding. 2. Memantine and cerestat produced complete inhibition of ACh-induced inward currents with affinities similar to that reported for native NMDA receptors. Cerestat, IC 50 1.7 (-1; +2) μM, was more potent than memantine, IC 50 5 (-3; +8) μM, and the effects of both drugs were fully and rapidly reversible. 3. Inhibition of α7 receptor function was voltage-independent, and it occurred at concentrations far lower than those needed to inhibit (never completely) binding of 125I-α-bgtx to α7 receptors, suggesting that the effects of memantine or cerestat are noncompetitive. 4. These results provide evidence that human α7 receptors are inhibited by memantine and cerestat and suggest that caution should be applied when using these compounds to study systems in which NMDA and nACh receptors co-exist.
U2 - 10.1038/sj.bjp.0705559
DO - 10.1038/sj.bjp.0705559
M3 - Article
C2 - 14645141
AN - SCOPUS:1642422286
VL - 140
SP - 1313
EP - 1319
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 7
ER -