Key result
Serotonin can be locally produced and degraded in the mammalian heart, exerting positive inotropic and chronotropic effects in transgenic mice and human atrial preparations.
Why the study?
Can serotonin (5-HT) be locally formed and degraded in the mammalian heart, and does it exert inotropic and chronotropic effects?
Can serotonin (5-HT) be locally formed and degraded in the mammalian heart, and does it exert inotropic and chronotropic effects?
The local production and degradation of serotonin in the mammalian heart can exert inotropic and chronotropic effects, which may be clinically relevant for unexplained arrhythmias.
May be relevant for unexplained arrhythmias; leaves open translation of cardiac serotonin effects to humans.
Using transgenic (TG) mice that overexpress the human serotonin (5-HT) 4a receptor specifically in cardiomyocytes, we wanted to know whether 5-HT can be formed and degraded in the mammalian heart and whether this can likewise lead to inotropic and chronotropic effects in this TG model. We noted that the 5-HT precursor 5-hydroxy-tryptophan (5-HTP) can exert inotropic and chronotropic effects in cardiac preparations from TG mice but not from wild-type (WT) mice; similar results were found in human atrial preparations as well as in intact TG animals using echocardiography. Moreover, by immunohistochemistry we could detect 5-HT metabolizing enzymes and 5-HT transporters in mouse hearts as well as in human atria. Hence, in the presence of an inhibitor of aromatic l-amino acid decarboxylase, the positive inotropic effects of 5-HTP were absent in TG and isolated human atrial preparations, and, moreover, inhibitors of enzymes involved in 5-HT degradation enhanced the efficacy of 5-HT in TG atria. A releaser of neurotransmitters increased inotropy in the isolated TG atrium, and this effect could be blocked by a 5-HT 4a receptor antagonist. Fluoxetine, an inhibitor of 5-HT uptake, elevated the potency of 5-HT to increase contractility in the TG atrium. In addition, inhibitors of organic cation and monoamine transporters apparently reduced the positive inotropic potency of 5-HT in the TG atrium. Hence, we tentatively conclude that a local production and degradation of 5-HT in the mammalian heart and more specifically in mammalian myocytes probably occurs. Conceivably, this formation of 5-HT and possibly impaired degradation may be clinically relevant in cases of unexplained tachycardia and other arrhythmias. NEW & NOTEWORTHY The present work suggests that inotropically active serotonin (5-HT) can be formed in the mouse and human heart and probably by cardiomyocytes themselves. Moreover, active degradation of 5-HT seems to occur in the mammalian heart. These findings may again increase the interest of researchers for cardiac effects of 5-HT.
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Gergs et al. (2017) studied this question. 5-hydroxy-tryptophan (5-HTP) and serotonin (5-HT) vs. Wild-type (WT) mice / baseline was evaluated on Inotropic and chronotropic effects. Serotonin can be locally produced and degraded in the mammalian heart, exerting positive inotropic and chronotropic effects in transgenic mice and human atrial preparations.
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