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Effects of antihistamines on the function of human α7-nicotinic acetylcholine receptors.
Eur J Pharmacol 2015; 746:308-16EJ

Abstract

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.

Authors+Show Affiliations

Laboratory of Functional Lipidomics, Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, UAE University, Abu Dhabi, Al Ain, United Arab Emirates.Laboratory of Functional Lipidomics, Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, UAE University, Abu Dhabi, Al Ain, United Arab Emirates.Laboratory of Functional Lipidomics, Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, UAE University, Abu Dhabi, Al Ain, United Arab Emirates.Department of Biological Sciences, Schmid College of Science and Technology, Chapman University, One University Drive, Orange, CA 92866, USA.College of Pharmacy, Al Ain University of Science and Technology, Al Ain, United Arab Emirates.College of Pharmacy, Al Ain University of Science and Technology, Al Ain, United Arab Emirates.Laboratory of Functional Lipidomics, Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, UAE University, Abu Dhabi, Al Ain, United Arab Emirates.Department of Biological Sciences, Schmid College of Science and Technology, Chapman University, One University Drive, Orange, CA 92866, USA.Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.Laboratory of Functional Lipidomics, Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, UAE University, Abu Dhabi, Al Ain, United Arab Emirates. Electronic address: Murat_Oz@uaeu.ac.ae.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25445036

Citation

Sadek, Bassem, et al. "Effects of Antihistamines On the Function of Human Α7-nicotinic Acetylcholine Receptors." European Journal of Pharmacology, vol. 746, 2015, pp. 308-16.
Sadek B, Khanian SS, Ashoor A, et al. Effects of antihistamines on the function of human α7-nicotinic acetylcholine receptors. Eur J Pharmacol. 2015;746:308-16.
Sadek, B., Khanian, S. S., Ashoor, A., Prytkova, T., Ghattas, M. A., Atatreh, N., ... Oz, M. (2015). Effects of antihistamines on the function of human α7-nicotinic acetylcholine receptors. European Journal of Pharmacology, 746, pp. 308-16. doi:10.1016/j.ejphar.2014.10.046.
Sadek B, et al. Effects of Antihistamines On the Function of Human Α7-nicotinic Acetylcholine Receptors. Eur J Pharmacol. 2015 Jan 5;746:308-16. PubMed PMID: 25445036.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2014/11/08/ PY - 2014/07/06/received PY - 2014/10/20/revised PY - 2014/10/22/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/9/1/medline KW - Antihistamine KW - Nicotinic acetylcholine receptor KW - Pyrilamine KW - Xenopus oocyte SP - 308 EP - 16 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 746 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. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/25445036/Effects_of_antihistamines_on_the_function_of_human_α7-nicotinic_acetylcholine_receptors L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(14)00753-5 DB - PRIME DP - Unbound Medicine ER -