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
Y1 - 2003
N2 - 1. Human alpha 7 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-alpha-bungarotoxin (125I-alpha-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, IC50 1.7 (-1; +2) microm, was more potent than memantine, IC50 5 (-3;+8) microM, and the effects of both drugs were fully and rapidly reversible. 3. Inhibition of alpha 7 receptor function was voltage-independent, and it occurred at concentrations far lower than those needed to inhibit (never completely) binding of 125I-alpha-bgtx to alpha 7 receptors, suggesting that the effects of memantine or cerestat are noncompetitive. 4. These results provide evidence that human alpha 7 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 alpha 7 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-alpha-bungarotoxin (125I-alpha-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, IC50 1.7 (-1; +2) microm, was more potent than memantine, IC50 5 (-3;+8) microM, and the effects of both drugs were fully and rapidly reversible. 3. Inhibition of alpha 7 receptor function was voltage-independent, and it occurred at concentrations far lower than those needed to inhibit (never completely) binding of 125I-alpha-bgtx to alpha 7 receptors, suggesting that the effects of memantine or cerestat are noncompetitive. 4. These results provide evidence that human alpha 7 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
SN - 0007-1188
VL - 140
SP - 1313
EP - 1319
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 7
ER -