Further characterization of agmatine binding to mitochondrial membranes: involvement of imidazoline I2 receptor

Agmatine, a divalent diamine with two positive charges at physiological pH, is transported into the matrix of liver mitochondria by an energy-dependent mechanism, the driving force of which is the electrical membrane potential. Its binding to mitochondrial membranes is studied by applying a thermodynamic treatment of ligand–receptor interactions on the analyses of Scatchard and Hill. The presence of two mono-coordinated binding sites S1 and S2, with a negative influence of S2 on S1, has been demonstrated. The calculated binding energy is characteristic for weak interactions. S1 exhibits a lower binding capacity and higher binding affinity both of about two orders of magnitude than S2. Experiments with idazoxan, a ligand of the mitochondrial imidazoline receptor I2, demonstrate that S1 site is localized on this receptor while S2 is localized on the transport system. S1 would act as a sensor of exogenous agmatine concentration, thus modulating the transport of the amine by its binding to S2.