Dissipation mechanisms for 5-hydroxytryptamine in the coronary circulation of the isolated perfused heart of the rat.
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 microM 5-HT (422 +/- 8.48 pmol g-1 min-1, n = 12) were reduced by pretreatment of the rats with 6-hydroxydopamine (22% inhibition), and by inclusion in the perfusion solution of 30 microM cocaine (28% inhibition), 100 microM 3-O-methylisoprenaline (64% inhibition), 100 microM corticosterone (58% inhibition), or 30 microM cocaine and 100 microM 3-O-methylisoprenaline (87% inhibition). 4. The extraneuronal deamination of 5-HT in the heart was saturable (Km = 101 microM, Vmax = 31.2 nmol g-1 min-1). The neuronal deamination of 5-HT was saturated by about 50 fold lower concentrations of 5-HT than was extraneuronal deamination, but Km and Vmax values could not be determined. 5. In 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.
Bryan
L J
LJ
Department of Physiology & Pharmacology, University of Queensland, Brisbane, Australia.
O'Donnell
S R
SR
Williams
A M
AM
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003326:Coronary Circulation / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D013563:Sympathectomy, Chemical
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D008995:Monoamine Oxidase