Effects of antihistamines on the function of human α7-nicotinic acetylcholine receptors
| Autor: | Tatiana R. Prytkova, Keun-Hang Susan Yang, Syed M. Nurulain, Murat Oz, Frank Christopher Howarth, Seyedeh Soha Khanian, Noor Atatreh, Bassem Sadek, Abrar Ashoor, Mohammad A. Ghattas |
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| Rok vydání: | 2015 |
| Předmět: |
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Molecular medicine.medical_specialty alpha7 Nicotinic Acetylcholine Receptor Molecular Conformation Nerve Tissue Proteins Pharmacology Xenopus laevis Allosteric Regulation Internal medicine Muscarinic acetylcholine receptor M5 Muscarinic acetylcholine receptor medicine Animals Humans Cells Cultured Acetylcholine receptor Pyrilamine Binding Sites Chemistry fungi Muscarinic acetylcholine receptor M3 Muscarinic acetylcholine receptor M2 Recombinant Proteins Protein Structure Tertiary Molecular Docking Simulation Kinetics Nicotinic acetylcholine receptor Endocrinology Nicotinic agonist Histamine H2 Antagonists Histamine H1 Antagonists Oocytes Ketamine Alpha-4 beta-2 nicotinic receptor Histamine H3 Antagonists |
| Zdroj: | European Journal of Pharmacology. 746:308-316 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2014.10.046 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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