New insights on receptor-dependent and monoamine oxidase-dependent effects of serotonin in the heart.

Abstract : Biogenic amines like serotonin (5-HT) and catecholamines usually act through stimulation of G-protein coupled receptors (GPCRs). We now have strong evidence that they can signal through receptor-independent mechanisms. One well described pathway is the degradation of biogenic amine by monoamine oxidases (MAOs) after transport into the cells by selective transporters. The oxidation of biogenic amines generates hydrogen peroxide, H(2)O(2), that can act as a signalling intermediate in the cell. This original mechanism of action of 5-HT is relevant in the heart since it is responsible for both cardiomyocyte hypertrophy and apoptosis. Moreover, in vivo experiments indicate a physiological significance for MAO in the damage during ischemia-reperfusion in the heart. Since functional 5-HT receptors are present in the heart and have also been demonstrated to contribute to cardiomyocyte growth and apoptosis, it is of major interest to evaluate respective contribution and cross-regulations between 5-HT receptors and MAO in cardiac function.