METABOLISM OF SEROTONIN IN MOUSE AND HUMAN HEART

Abstract

Serotonin (5‐HT) can exert cardiac effects like increase in force of contraction and increase in beating rate. It is generally assumed that 5‐HT is generated in non‐cardiac tissue and reaches the heart via the blood. However, we hypothesized that 5‐HT might be produced within the heart. Hence, we studied the effect of the direct precursor of 5‐HT, that is 5‐hydroxytryptophane. Indeed, 5‐hydroxytryptophane (1‐100 µM) exerted a concentration dependent increase in force of contraction and in beating rate in isolated left and right atrial preparations of transgenic mice overexpressing the human 5‐HT4‐receptor. But 5‐hydroxytryptophane was 30 to 100 fold less potent than 5‐HT. The effect could be blocked by pre‐incubation with an inhibitor (100 µM NSD 1015) of the pacemaker enzyme for formation of 5‐HT, that is aromatic L‐amino acid decarboxylase. Moreover, in isolated electrically driven (1 Hz) trabeculae (n=10) from five patients (undergoing bypass surgery), a positive inotropic effect to 100 µM 5‐hydroxytryptophane was noted which could be completely abolished by a 5‐HT4‐receptor antagonist (GR113808). These data combined argue for the possibility that intracardiac formation of serotonin can occur and might be relevant in health and disease.