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http://dx.doi.org/10.25673/102853
Title: | Cardiovascular effects of bufotenin on human 5‑HT4 serotonin receptors in cardiac preparations of transgenic mice and in human atrial preparations |
Author(s): | Neumann, Joachim Schulz, Nils Fehse, Charlotte Azatsian, Karyna Čináková, Aneta Marušáková, Margaréta Hofmann, Britt ![]() Gergs, Ulrich ![]() |
Issue Date: | 2023 |
Type: | Article |
Language: | English |
Abstract: | It is unclear whether bufotenin (= N,N-dimethyl-serotonin = 5-hydroxy-N,N-dimethyl-tryptamine), a hallucinogenic drug, can act on human cardiac serotonin 5-HT4 receptors. Therefore, the aim of the study was to examine the cardiac effects of bufotenin and for comparison tryptamine in transgenic mice that only express the human 5-HT4 receptor in cardiomyocytes (5-HT4-TG), in their wild-type littermates (WT) and in isolated electrically driven (1 Hz) human atrial preparations. In 5-HT4-TG, we found that both bufotenin and tryptamine enhanced the force of contraction in left atrial preparations (pD2 = 6.77 or 5.5, respectively) and the beating rate in spontaneously beating right atrial preparations (pD2 = 7.04 or 5.86, respectively). Bufotenin (1 µM) increased left ventricular force of contraction and beating rate in Langendorff perfused hearts from 5-HT4-TG, whereas it was inactive in hearts from WT animals, as was tryptamine. The positive inotropic and chronotropic effects of bufotenin and tryptamine were potentiated by an inhibitor of monoamine oxidases (50 µM pargyline). Furthermore, bufotenin concentration- (0.1–10 µM) and time-dependently elevated force of contraction in isolated electrically stimulated musculi pectinati from the human atrium and these effects were likewise reversed by tropisetron (10 µM). We found that bufotenin (10 µM) increased the phosphorylation state of phospholamban in the isolated perfused hearts, left and right atrial muscle strips of 5-HT4-TG but not from WT and in isolated human right atrial preparations. In summary, we showed that bufotenin can increase the force of contraction via stimulation of human 5-HT4 receptors transgenic mouse cardiac preparations but notably also in human atrial preparations. |
URI: | https://opendata.uni-halle.de//handle/1981185920/104806 http://dx.doi.org/10.25673/102853 |
Open Access: | ![]() |
License: | ![]() |
Journal Title: | Naunyn-Schmiedeberg's archives of pharmacology |
Publisher: | Springer |
Publisher Place: | Berlin |
Original Publication: | 10.1007/s00210-023-02414-8 |
Appears in Collections: | Open Access Publikationen der MLU |
Files in This Item:
File | Description | Size | Format | |
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s00210-023-02414-8.pdf | 2.77 MB | Adobe PDF | ![]() View/Open |