In the human cardiovascular system, serotonin (5-HT) exerts positive inotropic and chronotropic effects mediated by 5-HT receptors. Moreover, 5-HT receptor stimulation can cause arrhythmias in the human heart. Response to 5-HT can fade due to desensitization of the receptor system and/or activation of phosphodiesterases. In this study, we investigated a potential desensitization of the human 5-HT receptor expressed in the mouse heart. Therefore, we have used atrial preparations of transgenic (TG) mice with cardiac myocyte-specific overexpression of the human 5-HT receptor and their non-transgenic littermates (WT). Homologous (by 5-HT) and potentially heterologous (by isoprenaline) desensitization of the 5-HT receptor was investigated in atria of TG mice. 5-HT increased force of contraction in isolated electrically paced left atria and beating rate in spontaneously beating right atria only in preparations from TG but not from WT. Pre-treatment of isolated atria with high concentrations (10-600 μM) of 5-HT for 60 min attenuated the positive inotropic effects and the positive chronotropic effects of 5-HT in TG atria. Several inhibitors of desensitization including Zn, sucrose, and paroxetine were tested. Whereas sucrose was without any effect and Zn only was partially effective, paroxetine was able to inhibit desensitization favoring at least in part a G-protein receptor-coupled kinase-mediated mechanism of 5-HT receptor desensitization in the TG mouse heart. In addition, desensitization of ventricular 5-HT receptors was noted in isolated perfused hearts (Langendorff preparations) from TG mice. In summary, we show homologous desensitization of the 5-HT receptor in the heart of a transgenic mouse model possibly dependent on active G-protein receptor-coupled kinase. The exact mechanism and a potentially heterologous desensitization have to be elucidated by further investigations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.