5-HYDROXYTRYPTAMINE STIMULATES GLUCOSE-TRANSPORT IN CARDIOMYOCYTES VIA A MONOAMINE OXIDASE-DEPENDENT REACTION

This study deals with the effect of 5-hydroxytryptamine (5-HT; seroton in) on glucose transport in isolated rat cardiac myocytes. In these ce lls, 5-HT (10-300 mu M), as well as tryptamine, 5-methoxytryptamine an d dopamine, elicited a 3-5-fold increase in glucose transport, as comp ared with control. This effect was maximal after 90 min, and was conco mitant with a 1.8- and 1.5-fold increase in the amounts of glucose tra nsporters GLUT1 and GLUT4 at the cell surface of the cardiomyocytes, a s determined by using the photoaffinity label hyl)benzoyl]-1,3-bis-(D- mannos-4-yl)propyl-2-amine (H-3-ATB-BMPA). In contrast, 3-3000 mu M of the selective 5-HT receptor agonists 5-carboxyamido-tryptamine, alpha -methyl-serotonin, 2-methyl-serotonin or renzapride failed to stimulat e glucose transport. The effect of 5-HT was not affected by (i) the 5- HT receptor antagonists methysergide (1 mu M), ketanserin (1 mu M), cy proheptadine (1 mu M), MDL 72222 (1 mu M) or ICS 205-930 (3 mu M), nor by (ii) the adrenergic receptor antagonists prazosin (1 mu M), yohimb ine (1 mu M) or propranolol (5 mu M), nor by (iii) the dopaminergic an tagonists SCH 23390 (1 mu M) or haloperidol (1 mu M). The monoamine ox idase inhibitors clorgyline (1 mu M) and tranylcypromine (1 mu M) comp letely suppressed the effect of 5-HT, whereas the control and insulin- stimulated rates of glucose transport were unaffected. Addition of cat alase or glutathione diminished the 5-HT-dependent stimulation of gluc ose transport by 50%; these two factors are known to favour the degrad ation of H2O2 (which can be formed during the deamination of amines by monoamine oxidases). Glutathione also depressed the stimulatory actio n of exogenously added H2O2 (200 mu M) by 30%. Furthermore, in cells t reated with 5-HT, a time-dependent accumulation of 5-hydroxy-1H-indol- 3-ylacetic acid (a product of 5-HT metabolism via monoamine oxidases) was observed, which paralleled the changes in glucose transport. In co nclusion, the stimulation of glucose transport by 5-HT in cardiomyocyt es is not mediated by a 5-HT1, 5-HT2, 5-HT3 or 5-HT4 receptor, nor by an adrenergic or dopaminergic receptor, but is likely to occur through the degradation of 5-HT by a monoamine oxidase and concomitant format ion of H2O2.