Pham, Thanh Hoai and Abella, Lina Maria Rayo and Hadova, Katarina and Klimas, Jan and Dhein, Stefan and Pockes, Steffen and Schlicht, Jonas Manfred Albert and Hofmann, Britt and Kirchhefer, Uwe and Neumann, Joachim and Gergs, Ulrich (2025) Stimulation of histamine H1-receptors produces a positive inotropic effect in the human atrium. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 398 (6). pp. 7235-7250. ISSN 0028-1298, 1432-1912
Full text not available from this repository. (Request a copy)Abstract
There is a controversy whether histamine H-1-receptor activation raises or lowers or does not affect contractility in the human heart. Therefore, we studied stimulation of H-1-receptors in isolated electrically stimulated (one beat per second) human atrial preparations (HAP). For comparison, we measured force of contraction in left atrial preparations (LA) from mice with overexpression of the histamine H-1-receptor in the heart (H-1-TG). We detected the messenger ribonucleic acid (mRNA) expression of human histamine H-1-receptors in HAP. In LA from H-1-TG, each cumulatively applied concentration of histamine and a dual H-1/H-2-agonist called 2-(2-thiazolyl)-ethylamine (ThEA) caused a time-dependent initial negative inotropic effect followed over time by a lasting positive inotropic effect. Both effects were concentration-dependent in LA from H-1-TG. After 100 mu M cimetidine, 10 mu M histamine exercised a positive inotropic effect in HAP that was diminished by 10 mu M mepyramine, an H-1-receptor antagonist. The concentrations of mepyramine and cimetidine used here are based on the work of others and our own work (e.g., Guo et al. J Cardiovasc Pharmacol. 6:1210-5 1984, Rayo Abella et al. J Pharmacol Exp Ther. 389:174-185 2024). Similarly, we observed that ThEA (10 mu M, 30 mu M, 100 mu M cumulatively applied) induced a concentration- and time-dependent positive inotropic effect in HAP. In HAP, we detected never negative inotropic effects to either histamine or ThEA. The positive inotropic effects to ThEA in HAP were reduced by mepyramine. The positive inotropic effects of ThEA in LA from H-1-TG and in HAP were not accompanied by reductions in the time of tension relaxation. We conclude that stimulation of histamine H-1-receptors only increases and does not decrease force of contraction in the HAP in our patients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IN-VITRO EVALUATION; H-1 RECEPTOR; OVEREXPRESSION; HISTAPRODIFEN; AGONISTS; MOUSE; H1-RECEPTORS; EXPRESSION; CHANNELS; ANALOGS; Human histamine H-1-receptors; Transgenic mouse atrium; Human atrium; Force of contraction |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Mar 2026 07:15 |
| Last Modified: | 31 Mar 2026 07:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65210 |
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