TY - JOUR
T1 - Effects of antihistamines on the function of human α7-nicotinic acetylcholine receptors
AU - Sadek, Bassem
AU - Khanian, Seyedeh Soha
AU - Ashoor, Abrar
AU - Prytkova, Tatiana
AU - Ghattas, Mohammad A.
AU - Atatreh, Noor
AU - Nurulain, Syed M.
AU - Yang, Keun Hang Susan
AU - Howarth, Frank Christopher
AU - Oz, Murat
N1 - Publisher Copyright:
© 2014 Elsevier B.V. All rights reserved.
PY - 2015/1/5
Y1 - 2015/1/5
N2 - Effects of the histamine H1 receptor (H1R) antagonists (antihistamines), promethazine (PMZ), orphenadrine (ORP), chlorpheniramine (CLP), pyrilamine (PYR), diphenhydramine (DPH), citerizine (CTZ), and triprolidine (TRP) on the functional properties of the cloned α7 subunit of the human nicotinic acetylcholine receptor expressed in Xenopus oocytes were investigated. Antihistamines inhibited the α7-nicotinic acetylcholine receptor in the order PYR>CLP>TRP>PMZ>ORP≥DPH≥CTZ. Among the antihistamines, PYR showed the highest reversible inhibition of acetylcholine (100 μM)-induced responses with IC50 of 6.2 μM. PYR-induced inhibition was independent of the membrane potential and could not be reversed by increasing the concentration of acetylcholine. Specific binding of [125I] α-bungarotoxin, a selective antagonist for α7-nicotinic acetylcholine receptor, was not changed in the presence of PYR suggesting a non-competitive inhibition of nicotinic receptors. In line with functional experiments, docking studies indicated that PYR can potentially bind allosterically with the α7 transmembrane domain. Our results indicate that the H2-H4 receptor antagonists tested in this study (10 μM) showed negligible inhibition of α7-nicotinic acetylcholine receptors. On the other hand, H1 receptor antagonists inhibited the function of human α7-nicotinic acetylcholine receptor, with varying potencies. These results emphasize the importance of α7-nicotinic acetylcholine receptor for future pharmacological/toxicological profiling.
AB - Effects of the histamine H1 receptor (H1R) antagonists (antihistamines), promethazine (PMZ), orphenadrine (ORP), chlorpheniramine (CLP), pyrilamine (PYR), diphenhydramine (DPH), citerizine (CTZ), and triprolidine (TRP) on the functional properties of the cloned α7 subunit of the human nicotinic acetylcholine receptor expressed in Xenopus oocytes were investigated. Antihistamines inhibited the α7-nicotinic acetylcholine receptor in the order PYR>CLP>TRP>PMZ>ORP≥DPH≥CTZ. Among the antihistamines, PYR showed the highest reversible inhibition of acetylcholine (100 μM)-induced responses with IC50 of 6.2 μM. PYR-induced inhibition was independent of the membrane potential and could not be reversed by increasing the concentration of acetylcholine. Specific binding of [125I] α-bungarotoxin, a selective antagonist for α7-nicotinic acetylcholine receptor, was not changed in the presence of PYR suggesting a non-competitive inhibition of nicotinic receptors. In line with functional experiments, docking studies indicated that PYR can potentially bind allosterically with the α7 transmembrane domain. Our results indicate that the H2-H4 receptor antagonists tested in this study (10 μM) showed negligible inhibition of α7-nicotinic acetylcholine receptors. On the other hand, H1 receptor antagonists inhibited the function of human α7-nicotinic acetylcholine receptor, with varying potencies. These results emphasize the importance of α7-nicotinic acetylcholine receptor for future pharmacological/toxicological profiling.
KW - Antihistamine
KW - Nicotinic acetylcholine receptor
KW - Pyrilamine
KW - Xenopus oocyte
UR - http://www.scopus.com/inward/record.url?scp=84916899040&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84916899040&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2014.10.046
DO - 10.1016/j.ejphar.2014.10.046
M3 - Article
C2 - 25445036
AN - SCOPUS:84916899040
SN - 0014-2999
VL - 746
SP - 308
EP - 316
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -