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The synthesis of noradrenaline by isolated guinea-pig atria
Authors:R. J. Merrills and J. Offerman
Affiliation:Department of Pharmacology, Pfizer Limited, Sandwich, Kent
Abstract:1. The initial rate of formation of noradrenaline by isolated atria from a physiological concentration of tyrosine was measured. 2. Study of the time-course of the formation led to the conclusion that newly formed noradrenaline enters a fraction of the total pool. Synthesis and turnover was maintained for at least 1·5hr. In this time it was not possible to increase the concentration in the storage pool by employing high concentrations of precursor. 3. Preincubation of the tissue with noradrenaline resulted in an accumulation within the tissue and inhibited new formation. It is suggested that this indicates the existence of a physiological mechanism to limit the synthesis of noradrenaline, avoid saturation of storage sites and enable the `re-uptake' process to operate. 4. The amount of noradrenaline formed from 3-hydroxytyramine (dopamine) was considerably greater than from tyrosine. The kinetic constants of the reactions are in agreement with the view that hydroxylation of tyrosine to dihydroxyphenylalanine (dopa) is rate-limiting.
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