Gergs, U. and Bernhardt, G. and Buchwalow, I. B. and Edler, H. and Froeba, J. and Keller, M. and Kirchhefer, U. and Koehler, F. and Misslinger, N. and Wache, H. and Neumann, J. (2019) Initial Characterization of Transgenic Mice Overexpressing Human Histamine H-2 Receptors. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 369 (1). pp. 129-141. ISSN 0022-3565, 1521-0103
Full text not available from this repository. (Request a copy)Abstract
In an integrative approach, we studied the role of histamine H(2 )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 H-2 receptor in a cardiac-specific way, histamine exerted concentration- and time-dependent positive inotropic and positive chronotropic effects. Messenger RNA of the human H-2 receptor was only detected in transgenic mice. Likewise, immunohistology and autoradiography only gave signals in transgenic but not in wild-type cardiac preparations. Similarly, a positive inotropic and positive chronotropic effect was observed with histamine in echocardiography of living transgenic mice and isolated perfused hearts (Langen-dorff 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 and amthamine and antagonized by cimetidine. In summary, we generated a new model to study the physiologic and pathophysiologic cardiac role of the human H-2 receptor.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN 5-HT4 RECEPTOR; HEART-FAILURE; CARDIAC OVEREXPRESSION; STIMULATION; GENE; PHOSPHOLAMBAN; CONTRACTILITY; ACTIVATION; RESPONSES; AGONISTS; |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Apr 2020 12:32 |
| Last Modified: | 14 Apr 2020 12:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27263 |
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