Phase separation in solutions of noradrenaline and adenosine triphosphate: influence of bivalent cations and drugs

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Abstract
1 From aqueous solutions of biogenic amines, such as noradrenaline plus adenosine triphosphate (ATP), a second liquid phase spontaneously separates in the presence of small amounts of bivalent cations such as calcium. This separation is reversible and temperature-dependent; the concentration of amine and ATP in the bottom phase is several times higher than in the supernatant. 2 Analytical ultracentrifugation provides evidence that the second phase consists of high molecular weight aggregates of the amine and ATP. 3 The separated second phase of the noradrenaline-ATP system dissolves isothermally on addition of tyramine and amphetamine which in vivo are known to liberate biogenic monoamines and which have a low tendency to aggregate with ATP. The apparent molecular weights of noradrenaline-ATP aggregates are decreased by tyramine and amphetamine. Dopamine does not diminish the second phase and it can also form aggregates of high molecular weight with ATP. 4 Bivalent cations in high concentrations diminish or abolish the separation of a second phase. 5 Small amounts of reserpine affect phase separation. 6 It is concluded that the physico-chemical properties of aggregates of biogenic amines with ATP may be of importance for understanding the storage and release of the amines in vivo.