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http://dx.doi.org/10.25673/58188
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DC Field | Value | Language |
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dc.contributor.author | Neumann, Joachim | - |
dc.contributor.author | Binter, Maximilian Benedikt | - |
dc.contributor.author | Fehse, Charlotte | - |
dc.contributor.author | Marušáková, Margaréta | - |
dc.contributor.author | Büxel, Maren Luise | - |
dc.contributor.author | Kirchhefer, Uwe | - |
dc.contributor.author | Hofmann, Britt | - |
dc.contributor.author | Gergs, Ulrich | - |
dc.date.accessioned | 2022-01-21T09:16:55Z | - |
dc.date.available | 2022-01-21T09:16:55Z | - |
dc.date.issued | 2021 | - |
dc.identifier.uri | https://opendata.uni-halle.de//handle/1981185920/60139 | - |
dc.identifier.uri | http://dx.doi.org/10.25673/58188 | - |
dc.description.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. | eng |
dc.description.sponsorship | Publikationsfonds MLU | - |
dc.language.iso | eng | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.subject.ddc | 615 | - |
dc.title | Amitriptyline functionally antagonizes cardiac H2 histamine receptors in transgenic mice and human atria | eng |
dc.type | Article | - |
local.versionType | publishedVersion | - |
local.bibliographicCitation.journaltitle | Naunyn-Schmiedeberg's Archives of Pharmacology | - |
local.bibliographicCitation.volume | 394 | - |
local.bibliographicCitation.pagestart | 1251 | - |
local.bibliographicCitation.pageend | 1262 | - |
local.bibliographicCitation.publishername | Springer | - |
local.bibliographicCitation.publisherplace | Berlin | - |
local.bibliographicCitation.doi | 10.1007/s00210-021-02065-7 | - |
local.openaccess | true | - |
local.accessrights.dnb | free | - |
Appears in Collections: | Open Access Publikationen der MLU |
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File | Description | Size | Format | |
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Neumann2021_Article_AmitriptylineFunctionallyAntag.pdf | 1.46 MB | Adobe PDF | ![]() View/Open |