Metal Chelates in the Storage and Transport of Neurotransmitters: Interactions of Metal Ions With Biogenic Amines¹

Equilibrium studies on the interaction of biogenic amines with iron (Fe 2+ and Fe 3+ ) and magnesium (Mg 2+ ) were undertaken in an attempt to correlate the stabilities of metal‐amine chelates and the reported granule‐binding affinities of the biogenic amines. By means of potentiometric equilibrium measurements at 25°C and an ionic strength of 10 (KNO 3 ) the formation constants of the Fe 2+ chelates with norepinephrine (NE) and adenosine‐S‐triphosphate (ATP) were determined. Possible structures were derived for the co‐ordinate binding of Fe 2 + with NE. The interactions of Fe 2+ and Fe 2+ ‐ATP with NE were investigated and the formation of Fe 2+ ‐NE‐ATP (1:1:1) mixed ligand ternary chelate was proposed on the basis of the equilibrium data. Information obtained from chelation studies of Fe 2+ with pyrocatechol and ethanolamine taken together with the data obtained on the Fe 2+ ‐NE system indicated that the binding of Fe 2+ by NE was probably via the pyrocatechol moiety. Equilibrium constants for the binding of tyramine (TA) dopamine (DA) and NE with Mg 2+ were also determined. The equilibrium data obtained on the Mg 2+ ‐amine systems indicated a correlation between the metal‐amine binding affinities and the structure and amine‐release (and storage) activities of the biogenic amines. A consideration of the stabilities of the Fe 2+ and Mg 2+ chelates together with the occurrence of these metal ions in synaptosomes suggests their possible involvement in the intra vesicular amine‐binding and storage sites.