Please use this identifier to cite or link to this item:
http://dx.doi.org/10.25673/58188
Title: | Amitriptyline functionally antagonizes cardiac H2 histamine receptors in transgenic mice and human atria |
Author(s): | Neumann, Joachim Binter, Maximilian Benedikt Fehse, Charlotte Marušáková, Margaréta Büxel, Maren Luise Kirchhefer, Uwe Hofmann, Britt Gergs, Ulrich |
Issue Date: | 2021 |
Type: | Article |
Language: | English |
Abstract: | We have previously shown that histamine (2-(1H-imidazol-4-yl)ethanamine) exerted concentration-dependent positive inotropic effects (PIE) or positive chronotropic effects (PCE) on isolated left and right atria, respectively, of transgenic (H2R-TG) mice that overexpress the human H2 histamine receptor (H2R) in the heart; however, the effects were not seen in their wild-type (WT) littermates. Amitriptyline, which is still a highly prescribed antidepressant drug, was reported to act as antagonist on H2Rs. Here, we wanted to determine whether the histamine effects in H2R-TG were antagonized by amitriptyline. Contractile studies were performed on isolated left and right atrial preparations, isolated perfused hearts from H2R-TG and WT mice and human atrial preparations. Amitriptyline shifted the concentration-dependent PIE of histamine (1 nM–10 μM) to higher concentrations (rightward shift) in left atrial preparations from H2R-TG. Similarly, in isolated perfused hearts from H2R-TG and WT mice, histamine increased the contractile parameters and the phosphorylation state of phospholamban (PLB) at serine 16 in the H2R-TG mice, but not in the WT mice. However, the increases in contractility and PLB phosphorylation were attenuated by the addition of amitriptyline in perfused hearts from H2R-TG. In isolated electrically stimulated human atria, the PIE of histamine that was applied in increasing concentrations from 1 nM to 10 μM was reduced by 10-μM amitriptyline. In summary, we present functional evidence that amitriptyline also acts as an antagonist of contractility at H2Rs in H2R-TG mouse hearts and in the human heart which might in part explain the side effects of amitriptyline. |
URI: | https://opendata.uni-halle.de//handle/1981185920/60139 http://dx.doi.org/10.25673/58188 |
Open Access: | ![]() |
License: | ![]() |
Sponsor/Funder: | Publikationsfonds MLU |
Journal Title: | Naunyn-Schmiedeberg's Archives of Pharmacology |
Publisher: | Springer |
Publisher Place: | Berlin |
Volume: | 394 |
Original Publication: | 10.1007/s00210-021-02065-7 |
Page Start: | 1251 |
Page End: | 1262 |
Appears in Collections: | Open Access Publikationen der MLU |
Files in This Item:
File | Description | Size | Format | |
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Neumann2021_Article_AmitriptylineFunctionallyAntag.pdf | 1.46 MB | Adobe PDF | ![]() View/Open |