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  • Title: Influence of neuronal uptake on the presynaptic alpha-adrenergic modulation of noradrenaline release.
    Author: Enero MA.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 1984 Nov; 328(1):38-40. PubMed ID: 6096727.
    Abstract:
    Conditions required for the inhibitory feedback modulation of noradrenergic neurotransmission were studied in isolated atria of the rat. The alpha adrenergic antagonist, yohimbine, 0.8 microM, or phentolamine, 1 microM, did not affect the chronotropic response to 4 or 8 shocks at 0.8 Hz but increased it when a higher number of shocks was applied. When neuronal uptake was inhibited by cocaine, 2.9 microM, or desipramine, 0.1 microM, the enhancement of neurotransmission by yohimbine or phentolamine was higher than that observed in the presence of alpha-adrenergic antagonists alone. In atria preincubated with 3H-noradrenaline, the effect of the drugs on the 3H-overflow evoked by 240 shocks at 2.0 Hz was studied. Cocaine 2.9 microM, did not increase the evoked overflow but yohimbine, 0.8 microM, did. The 3H-overflow obtained in the group of yohimbine plus cocaine was significantly higher than was expected from the effects of both drugs alone. It is concluded that yohimbine or phentolamine enhance the chronotropic response in rat atria only when the concentration of noradrenaline in the biophase is sufficiently high to activate presynaptic receptors. In this tissue, the efficiency of the neuronal uptake influences the degree of alpha-adrenergic autoinhibition.
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