Production and Function of Serotonin in Cardiac Cells

Abstract

Serotonin [5-hydroxy-tryptamine (5-HT)] exerts a number of effects in the mammalian heart: increase in heart rate, increase in force of contraction, fibrosis of cardiac valves, coronary constriction, arrhythmias and thrombosis. These effects are, in part, mediated by 5-HT-receptors, in part, directly by 5-HT action on intracellular proteins. In the beginning, 5-HT was thought to be only produced in the gut and then transported into the heart via platelets, because platelets can take up 5-HT in the gut and enter the capillaries and thus the mammalian heart. 5-HT is to a large extent metabolized in the liver and excreted via the urine. Here, we will also overview data that argue for additional pathways, namely production and degradation of 5-HT in the cells of the heart itself.

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H2Receptors

“…We ourselves encountered a similar finding several years ago: when studying the effects of serotonin in human cardiac preparations (Gergs et al, 2009) we noted unexpectedly that under the very same experimental conditions where we noted a PIE of serotonin, mediated by 5HT 4 receptors, using human right atrial preparations in the organ bath, we failed to detect a similar effect in mouse atrial preparations (Läer et al, 1998). Hence, we generated mice that express a functional human 5HT 4 receptor and studied these mice in some detail (Gergs et al, 2010Neumann et al, 2017). We showed a PCE and PIE in atrial preparations to serotonin in these transgenic mice .…”

Influence of Serotonin 5-HT4 Receptors on Responses to Cardiac Stressors in Transgenic Mouse Models

“…Peripheral organs, such as the intestinal wall [ 3 ], contain 95% of the total amount of 5-HT in the body [ 4 ]; from there, the 5-HT can be taken up by various blood cells and transported mainly by thrombocytes to the heart [ 5 , 6 ]. In addition, 5-HT can also be synthesized in the heart, most notably in cardiomyocytes [ 7 , 8 ].…”

“…5-HT can lead to vasoconstriction and subsequent hypertension [ 1 , 9 , 10 ], although it can also directly affect the cells in the heart. It is also known to increase the force of contraction and, thus, has a positive inotropic effect (PIE) on the atrium and the ventricle of some mammals, including humans [ 7 , 11 , 12 , 13 ]. Moreover, 5-HT can increase the heart rate by acting on cells in the sinus node in isolated human preparations [ 14 , 15 ] and isolated pig atrium samples [ 16 ]; thus, 5-HT has a positive chronotropic effect (PCE).…”

Investigation of cardiorespiratory effects of the selective 5‐HT4 agonist BIMU‐8 in etorphine‐immobilised goats (Capra aegagrus hircus) in a randomized, blinded and controlled trial

“…Within 2 minutes of administration, BIMU‐8 led to a mean HR of 118 (±7) beats per minute, a 73% increase from baseline. Although this increase in HR might be part of a baroreflex response, given the initial fall, then return to pre‐etorphine levels of MAP, there is evidence that suggests direct cardiac 5‐HT4 receptor activation increases HR 27,28 . Activation of 5‐HT4 receptors is thought to initiate a cascade via G‐proteins, adenylyl cyclase, cAMP and then activating cyclic nucleotidegated cation channels (HCN) in the sinus node 28 …”