| Autor: |
Matsumoto, Yuichi, Funahashi, Jun, Mori, Kiyotoshi, Hayashi, Kozue, Yano, Hiroshi |
| Předmět: |
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| Zdroj: |
Pharmacology; 2007, Vol. 81 Issue 3, p266-274, 9p, 2 Diagrams, 1 Chart, 3 Graphs |
| Abstrakt: |
Calcium responses to various concentrations of histamine were monitored in Chinese hamster ovary cells stably expressing the human histamine H1 receptor. The effects of various histamine H1 receptor antagonists on the dose-response curve for histamine were evaluated. Olopatadine hydrochloride (olopatadine) inhibited the histamine-induced maximum response (pD2’: 7.5) but had insignificant effects on histamine EC50 values. This noncompetitive property exhibited by olopatadine, which was also observed in human umbilical vein endothelial cells, was the most striking among the antihistamines tested in this study. The geometrical isomer of olopatadine (E-isomer), which had a similar binding affinity to the histamine H1 receptor as olopatadine, showed a mixed antagonistic profile (competitive and noncompetitive). These results indicate that the geometry around the double bond in the dimethylaminopropylidene group is critical for the potent noncompetitive property of olopatadine. Furthermore, binding mode analyses suggest that the protonated amine group in the dimethylaminopropylidene moiety of olopatadine forms an ionic bond with Glu 181 that is present in the second extracellular loop of the histamine H1 receptor, whereas the amine group of the E-isomer does not. The second extracellular loop in aminergic G-protein-coupled receptors contributes to ligand binding and therefore the noncompetitive property of olopatadine may be explained by the interaction with Glu 181. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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