Chamber-specific alterations of noradrenaline uptake (uptake(1)) in right ventricles of monocrotaline-treated rats.
1. In rats a single injection of the alkaloid monocrotaline (60 mg MCT kg(-1) body weight, i.p.) caused right ventricular hypertrophy and heart failure. The aim of this study was to find out whether, in these MCT-treated rats, the cardiac neuronal noradrenaline uptake (uptake(1)) might undergo chamber-specific alterations. 2. For this purpose we assessed in right and left ventricular slices, uptake(1) activity (by [(3)H]-noradrenaline accumulation), and in right and left ventricular membranes, uptake(1) carrier protein density (by [(3)H]-nisoxetine binding). 3. Uptake(1)-inhibitors blocked [(3)H]-noradrenaline accumulation in ventricular slices and [(3)H]-nisoxetine binding in ventricular membranes with the order of potency: desipramine > nisoxetine >> cocaine > or = GBR 12909, indicating that with both approaches noradrenaline uptake(1) was determined. 4. In right ventricular slices of MCT-treated rats uptake(1) activity was significantly lower than in control rats (84.7+/-8.2 vs 145.1+/-6.2 pmol noradrenaline mg(-1) tissue 15 min(-1); P<0.05). This was accompanied by a significant decrease in the density of [(3)H]-nisoxetine binding sites (73.7+/-14.4 vs 125.9+/-9.1 fmol mg(-1) protein; P:<0.05). 5. In left ventricular slices of MCT-treated rats uptake(1) activity was not significantly altered (131.2+/-10.5 vs 116.1+/-5.2 pmol noradrenaline mg(-1) tissue 15 min(-1)); similarly, also the density of [(3)H]-nisoxetine binding sites was unchanged (108+/-9.7 vs 123+/-7.7 fmol mg(-1) protein). 6. We conclude that in MCT-treated rats with right ventricular hypertrophy and heart failure uptake(1) activity is chamber-specifically reduced possibly due to a decrease in carrier protein density.
Leineweber
K
K
Institute of Pharmacology and Toxicology, University of Halle-Wittenberg, Halle/Saale, Germany.
Seyfarth
T
T
Brodde
O E
OE
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006984:Hypertrophy; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D016686:Monocrotaline / Q000494:pharmacology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium
D018759:Adrenergic Uptake Inhibitors; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D005473:Fluoxetine; D014316:Tritium; C011386:nisoxetine; D016686:Monocrotaline; C043425:vanoxerine; D003042:Cocaine; D003891:Desipramine; D009638:Norepinephrine