Monoamine oxidase (MAO) is inhibited by imidazoline binding site I₂ specific ligands in vitro

Two types of imidazoline binding sites (I₁- and I₂-BS) were identified until now and less is known about their function, especially about I₂-BS. The hypothesis of the present study was that I₂-BS ligands affect monoamine oxidase (MAO) activity because I₂-BS was found to be located on mitochondria. Therefore, different imidazoline-, imidazole- and guanidinederivatives and α-adrenoceptor ligands were taken with regard to their ability to affect MAO activity in vitro. Enzyme kinetic was established in the presence of inhibitors (10^-6-10^-2 M). We found that MAO activity was decreased relatively to maximum effects (without inhibitors) significantly at concentration of 100 μM/l by substances with high affinity to I₂-BS (antazoline: -76.5, idazoxan: -70.1, cirazoline: -64.1) than by I₁-ligands (efaroxan: -15.1, rilmenidine: -31.2, clonidine: -12.0, moxonidine: -8.2). Substances with highest inhibitory effect were BDF 8082 (-93.2) and 2-(2-benzofuranyl)-2 -imidazoline (-90.9). Agmatine, the endogenous ligand at IBS, also decreased MAO activity (-35.6) whereas its precursor L-arginine had no effect. The mechanism of inhibition is non-competitive because v(max) but not k(m) was affected. From our data we conclude that the reduction in MAO activity following blockade of I₂- BS confirms our hypothesis of an I₂ regulatory binding site at MAO and therefore its functional importance.