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• W4366724624 abstract "Abstract Introduction Ergometrine (6a R ,9 R )- N -(( S )-1-Hydroxypropan-2-yl)-7-methyl-4,6,6a,7,8,9-hexa-hydro-indolo-[4,3- fg ]chinolin-9-carboxamide or lysergide acid β-ethanolamide or ergonovine) activates several types of serotonin and histamine receptors in the animal heart. We tested the hypotheses that ergometrine might activate human serotonin 5-HT 4 receptors (h5-HT 4 R) and/or human histamine H 2 receptors (hH 2 R) in the heart of transgenic mice and/or in the human isolated atrium. Methods Force of contraction or beating rates were studied in electrically stimulated left atrial or spontaneously beating right atrial preparations or spontaneously beating isolated retrogradely perfused hearts (Langendorff-set up) of mice with cardiac specific overexpression of the h5-HT 4 R (5-HT 4 -TG) or of mice with cardiac specific overexpression of the hH 2 R (H 2 -TG) or in electrically stimulated human right atrial preparations obtained during cardiac surgery. Western blots to assess phospholamban (PLB) phosphorylation on serine 16 were performed. Results Ergometrine exerted concentration- and time-dependent positive inotropic effects and positive chronotropic effects in atrial preparations starting at 0.3 µM and reaching a plateau at 10 µM in H 2 -TGs (n = 7). This was accompanied by an increase in PLB phosphorylation at serine 16. Ergometrine up 10 µM failed to increase force of contraction in left atrial preparations from 5-HT 4 -TGs (n = 5). 10 µM ergometrine increased the force of contraction in isolated retrogradely perfused spontaneously beating heart preparations (Langendorff set-up) from H 2 -TG but not 5-HT 4 -TG. In the presence of the phosphodiesterase inhibitor cilostamide (1 µM), 10 µM ergometrine exerted positive inotropic effects in isolated electrically stimulated human right atrial preparations, obtained during cardiac surgery, and these effects were attenuated by 10 µM of the H 2 R antagonist cimetidine but not by 10 µM of the 5-HT 4 R antagonist tropisetron. Furthermore, ergometrine showed binding to human histamine H 2 receptors (at 100 µM and 1 mM) using HEK cells in a recombinant expression system (p K i < 4.5, n = 3). Conclusion Ergometrine is an agonist at cardiac human H 2 Rs." @default.
• W4366724624 created "2023-04-24" @default.
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• W4366724624 date "2023-04-21" @default.
• W4366724624 modified "2023-09-26" @default.
• W4366724624 title "Ergometrine stimulates histamine H 2 receptors in the isolated human atrium" @default.
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• W4366724624 doi "https://doi.org/10.21203/rs.3.rs-2832272/v1" @default.
• W4366724624 hasPublicationYear "2023" @default.
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