Ionophoric Properties of Angiotensin II Peptides. Nuclear Magnetic Resonance Kinetic Studies of the Hormone-Mediated Transport of Manganese Ions Across Phosphatidylcholine Bilayers

The linear peptide hormones angiotensin II and [Asn¹, Val⁵] angiotensin II are found to mediate the transport of Mn(II) ions across phosphatidylcholine bilayers. Nuclear magnetic resonance spectroscopy (NMR) is applied to monitor the rate of transport of Mn(II) ions by measuring the rate of disappearance of the NMR signal of the choline methyl groups of the inner phospholipid layer. This rate of disappearance is analyzed in terms of a pseudo-first-order rate equation for the transport process. The rate of transport of Mn(II) varies linearly with both the concentrations of Mn(II) and angiotensin II (A-II) present, suggesting that the ions are transported in a complex with 1:1 stoichiometry. An analysis of the temperature dependence of the rate of transport yielded an energy of activation of 29 ± 5 kcal/mol and an entropy of activation of 10 eu for the transport process. The activation parameters are discussed in terms of defining the rate-limiting step in the transport process. The pH dependence of the hormone-mediated rate of Mn(II) transport is similar to the pH dependence of the metal complexation process measured in a separate study. The presence of La(III) or Tris decelerates the rate of Mn(II) transport by presumably competing with either Mn(II) or A-II, respectively, in the binding process. On the basis of the results presented here as well as literature data, we suggest that the ionophoric properties of these two hormones may be relevant to understanding the role of metal ions in their physiological activities.