Friedgen, Bernd and Wölfel, Reinhard and Russ, Hermann and Schömig, Edgar and Graefe, Karl-Heinz (1996) The role of extraneuronal amine transport systems for the removal of extracellular catecholamines in the rabbit. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 354 (3). pp. 275-286. ISSN 0028-1298, 1432-1912
Full text not available from this repository.Abstract
As selective inhibitors of the extraneuronal monoamine uptake system (uptake(2)) suitable for in-vivo studies were not available, the question of whether uptake(2) plays a definite role in vivo is largely unresolved. We attempted to resolve the question by using 1,1'-diisopropyl-2,4'-cyanine iodide (disprocynium24), a novel agent that blocks uptake(2) in vitro with high potency. Anaesthetized rabbits were infused with H-3-labelled noradrenaline, adrenaline and dopamine, and catecholamine plasma clearances as well as rates of spillover of endogenous catecholamines into plasma were measured before and during treatment with either disprocynium24 or vehicle, Four groups of animals were studied: group I, no further treatment; group II, monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) inhibited; group III, neuronal uptake (uptake(1)) inhibited; group IV, uptake(1) as well as MAO and COMT inhibited. Disprocynium24 (270 nmol kg(-1) i.v. followed by an i.v. infusion of 80 nmol kg(-1) min(-1)) did not alter heart rate and mean arterial blood pressure, but increased cardiac output by 22% and decreased the total peripheral vascular resistance by 16% with no difference between groups. When compared with vehicle controls, catecholamine clearances (normalized for the cardiac output of plasma) were decreased and spillover rates increased in response to disprocynium24. Although there were statistically significant between-group differences in baseline clearances (which decreased in the order: group I > group II > group III > group IV), the drug-induced clearance reductions relative to vehicle controls were similar in groups I to IV and amounted to 29-38% for noradrenaline, 22-31% for adrenaline and 16-22% for dopamine. Hence, there was still a significant % reduction in catecholamine clearances even after the combined inhibition of MAO and COMT, and there was no increase in the % reduction of clearances after inhibition of uptake(1). Noradrenaline spillover increased in response to disprocynium24 in all four groups by 1.6- to 1.9-fold, whereas a 1.5- to 2.0-fold increase in adrenaline and dopamine spillover was observed in groups II and IV only. The results indicate that disprocynium24 interferes with the removal of circulating catecholamines not only by inhibiting uptake(2), but also by inhibiting related organic cation transporters. As disprocynium24 increased the spillover of endogenous catecholamines into plasma even after inhibition of MAO and COMT, organic cation transporters may also be involved in the removal of endogenous catecholamines before they enter the circulation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SYMPATHETIC-NERVE ACTIVITY; INTRASYNAPTIC NOREPINEPHRINE CONCENTRATIONS; NORADRENALINE TRANSPORT; PERFUSED LUNGS; O-METHYLATION; PLASMA; DESIPRAMINE; HUMANS; 3,4-DIHYDROXYPHENYLALANINE; ADRENALINE; plasma clearance of catecholamines; MAO-inhibition; COMT-inhibition; disprocynium24; uptake(2); organic cation transporters |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Nov 2023 05:33 |
| Last Modified: | 02 Nov 2023 05:33 |
| URI: | https://pred.uni-regensburg.de/id/eprint/51578 |
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