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  • Title: Evidence for neuronal uptake and release of norfenefrine and evaluation of its alpha-agonistic effects in the rabbit pulmonary artery.
    Author: Reimann W.
    Journal: Arzneimittelforschung; 1984; 34(5):575-8. PubMed ID: 6147146.
    Abstract:
    Rabbit pulmonary artery strips were used for the evaluation of the alpha 1-/alpha 2-agonistic activity of norfenefrine (active principle of the antihypotensive agent Novadral) and for the investigation of neuronal uptake and release mechanisms for norfenefrine in the vessel wall. At 0.1 and 1 mumol/l, norfenefrine caused contractions of the artery strips, while presynaptic inhibition of stimulation-evoked noradrenaline release could not be detected with certainty. Thus, in the range tested, alpha 1-agonistic activity was more pronounced. Uptake and release of 3H-norfenefrine was studied on noradrenaline-depleted arteries. Rabbits were pretreated either with alpha-methyl-p-tyrosine (metirosine, alpha-MT) to inhibit noradrenaline synthesis without affecting storage vesicle function or with reserpine to eliminate vesicular storage capacity. In arteries from animals pretreated with alpha-MT, more substance was retained after preincubation with 3H-norfenefrine, in comparison with reserpine pretreated arteries, and about 2% of the substance was released from Arteries from reserpine pretreated animals retained less 3H-norfenefrine after preincubation, in comparison with alpha-MT pretreated arteries, and less than 0.2% was released per stimulation period. After alpha-MT treatment, tension developed upon stimulation was enhanced after norfenefrine preincubation, while contractions of reserpine pretreated arteries were independent of norfenefrine preincubation. These results provide evidence for an uptake of norfenefrine in the noradrenaline storage vesiculation period. After alpha-MT treatment, tension developed upon stimulation was enhanced after norfenefrine preincubation, while contractions of reserpine pretreated arteries were independent of norfenefrine preincubation. These results provide evidence for an uptake of norfenefrine in the noradrenaline storage vesicles and a vesicular co-secretion of norfenefrine with noradrenaline upon stimulation. The impaired sympathetic transmission was thereby improved.
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