1 The contribution of uptake into vascular endothelial cells, of neuronal uptake and of extraneuronal uptake in the dissipation of 5-hydroxytryptamine (5-HT) perfused through the coronary circulation of the rat heart was examined. 2 Hearts from reserpine-pretreated rats were isolated and perfused in vitro with 5-HT, in the absence or presence of inhibitors, and rates of appearance of the deaminated metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in the venous effluent were measured using an h.p.l.c. assay. 3 The steady-state rates of 5-HIAA appearance in the venous effluent in hearts perfused with 1 JM 5-HT (422 + 8.48 pmol g min, n = 12) were reduced by pretreatment of the rats with 6-hydroxydopamine (22% inhibition), and by inclusion in the perfusion solution of 30 yM cocaine (28% inhibition), 100pM 3-0-methylisoprenaline (64% inhibition), 100pM corticosterone (58% inhibition), or 30OuM cocaine and 100pM 3-0-methylisoprenaline (87% inhibition). 4 The extraneuronal deamination of 5-HT in the heart was saturable (Km = 101 M, V,,,,, = 31.2 nmol g-min 1). The neuronal deamination of 5-HT was saturated by about 50 fold lower concentrations of 5-HT than was extraneuronal deamination, but K, and V,. values could not be determined.
5In the coronary circulation of the rat heart, 5-HT was dissipated by the uptake processes for catecholamines, extraneuronal uptake (predominantly) and neuronal uptake, and subsequent metabolism by monoamine oxidase. There was no evidence that a cocaine-sensitive uptake of 5-HT into vascular endothelial cells made any significant contribution to 5-HT dissipation in the heart.