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J Pharmacol Exp Ther. 2019 Feb 6. pii: jpet.118.255711. doi: 10.1124/jpet.118.255711. [Epub ahead of print]

Initial characterization of transgenic mice overexpressing human histamine H2 receptors.

Author information

1
University Hospital Halle.
2
Chemistry Regensburg.
3
Pathology Hamburg.
4
Chemie Regensburg.
5
University Hospital Muenster.
6
University Hospital Halle; joachim.neumann@medizin.uni-halle.de.

Abstract

In an integrative approach, we studied the role of H2 receptors in the mouse heart. We noted that histamine, added cumulatively to the organ bath, failed to affect the force of contraction in left atrial preparations and did not change spontaneous heart rate in right atrial preparations from wild type mice. By contrast, in the same preparations from mice that overexpressed the human H2 receptor in a cardiac specific way, histamine exerted concentration and time dependent positive inotropic and positive chronotropic effects. Messenger RNA of the human H2 receptor was only detected in transgenic mice. Likewise, immunohistology and autoradiography only gave signals in transgenic and not in wild type cardiac preparations. Similarly, a positive inotropic and positive chronotropic effect was observed with histamine in echocardiography of living transgenic mice or in isolated perfused hearts (Langendorff preparation). Phosphorylation of phospholamban was increased in atrial and ventricular preparations from transgenic mice, but not in wild type animals. The effects of histamine were mimicked by dimaprit or amthamine and antagonized by cimetidine. In summary, we generated a new model to study the physiological and pathophysiological cardiac role of the human H2 receptor.  .

KEYWORDS:

cardiovascular drugs; histamine; histamine receptors; transgenic mice

PMID:
30728249
DOI:
10.1124/jpet.118.255711
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