Histamine is metabolized by several enzymes in vitro and in vivo. The relevance of this
metabolism in the mammalian heart in vivo is unclear. However, histamine can exert
positive inotropic effects (PIE) and positive chronotropic effects (PCE) in humans via H2-
histamine receptors. In transgenic mice (H2-TG) that overexpress the human H2 receptor in
cardiomyocytes but not in wild-type littermate mice (WT), histamine induced PIE and PCE
in isolated left or right atrial preparations. These H2-TG were used to investigate the
putative relevance of histamine degrading enzymes in the mammalian heart. Histidine, the
precursor of histamine, increased force of contraction (FOC) in human atrial preparations.
Moreover, histamine increased the phosphorylation state of phospholamban in human
atrium. Here, we could detect histidine decarboxylase (HDC) and histamine itself in
cardiomyocytes of mouse hearts. Moreover, our data indicate that histamine is subject
to degradation in the mammalian heart. Inhibition of the histamine metabolizing enzymes
diamine oxidase (DAO) and monoamine oxidase (MAO) shifted the concentration response
curves for the PIE in H2-TG atria to the left. Moreover, activity of histamine metabolizing
enzymes was present in mouse cardiac samples as well as in human atrial samples. Thus,
drugs used for other indication (e.g. antidepressants) can alter histamine levels in the heart.
Our results deepen our understanding of the physiological role of histamine in the mouse
and human heart. Our findings might be clinically relevant because we show enzyme
targets for drugs to modify the beating rate and force of the human heart.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84406 |
| Date | 30 March 2023 |
| Creators | Neumann, Joachim, Grobe, Juliane M., Weisgut, Jacqueline, Schwelberger, Hubert G., Fogel, Wieslawa Agnieszka, Marusˇáková, Margaréta, Wache, Hartmut, Bähre, Heike, Buchwalow, Igor B., Dhein, Stefan, Hofmann, Britt, Kirchhefer, Uwe, Gergs, Ulrich |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1663-9812, 582916 |
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