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

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.