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  • Title: Effect of blockade of noradrenaline re-uptake on evoked tritium overflow from mouse vasa deferentia and rat cortex slices.
    Author: el-Mas M, Hughes IE.
    Journal: Br J Pharmacol; 1990 Nov; 101(3):762-8. PubMed ID: 2076491.
    Abstract:
    1. In tissues previously incubated with [3H]-noradrenaline exposure to cocaine (0.1 to 10 microM) or desmethylimipramine (0.01 to 1 microM) produced a concentration-dependent increase (up to 2 fold) in electrically evoked (3 Hz, 2 ms, 20 mA, 120s every 20 min) fractional overflow of tritium from rat brain cortex slices but not from mouse vas deferens (2.5 Hz, 2 ms, 400 mA, for 90s every 14 min). 2. Yohimbine and idazoxan (0.01 to 1 microM) increased fractional evoked overflow of tritium by up to 2 fold; in the presence of these drugs, cocaine (10 microM) produced an increase in both tissues (up to 3.5 fold over control). 3. In brain slice an increase in stimulation frequency (0.1, 0.5, 1, 3 and 6 Hz) decreased fractional evoked overflow of tritium per pulse but cocaine (10 microM) produced a significant enhancement at each frequency except 6 Hz. In vas deferens fractional tritium overflow per pulse changed little with increasing frequency and cocaine produced no effect. 4. In both tissues fractional evoked overflow of tritium was dependent on the stimulation current; cocaine (10 microM) increased fractional evoked overflow from brain slice at every current tested but was without effect in vas deferens. 5. Chromatographic separation of the released tritium showed there was little difference in the proportions of [3H]-noradrenaline and 3H-metabolites overflowing from the tissues. Cocaine increased the proportion of [3H]-noradrenaline and decreased the proportion of [3H]-DOPEG overflowing both at rest and during stimulation. 6. In brain slice an increase in electrically evoked overflow was produced by cocaine (10 microM) whether total tritium overflow (1.8 fold), overflow of [3H]-noradrenaline (1.8 fold) or overflow of unlabelled noradrenaline (1.8 fold) was measured. Evoked overflow from vas deferens was unaffected when assessed by any of these three methods. 7. The mechanism responsible for this differential effect of cocaine is unclear but may involve differences in the physical relationship between release sites, reuptake sites and presynaptic autoreceptors.
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