Relationship between I2 imidazoline binding sites and monoamine oxidase B in liver

Biochemical and pharmacologic studies suggest that I,imidazoline binding sites (I2BS) represent a heterogeneous family of membrane proteins. Indeed, the imidazoline binding sites located on monoamine oxidases (MAO) A and B display different pharmacologic properties. Recent results suggest that in liver and brain, I2BS may be located on proteins distinct from MAOs. The following observations indicate that in liver and brain, [H-3]idazoxan binds exclusively to I2BS located on MAO-B: (1) size exclusion chromatography of digitonin-solubilized preparations from rabbit and human liver showed that CIilldazoxan-specific binding eluted only in two peaks (similar to 175,000 and similar to 100,000 Da,corresponding to 90% and 10% of the recovered [H-3]idazoxan binding) which also contained MAOs as determined by [C-14]tyramine oxidation and Western blot analysis; (2) according to previous results obtained in various human and rat tissues, experiments performed in mice liver and brain showed that idazoxan was a potent inhibitor of [I-125]-AZIPI photoincorporation; to MAO-B but not to MAO-A; (3) in MAO-deficient transgenic mice, [H-3]idazoxan binding to liver and brain membranes was completely abolished in MAO-B knockout mice and was not affected in MAO-A knockout mice. Together, these results show that in both liver and brain, I,BS are located exclusively on MAO-B; The imidazoline binding site on MBO-A, which photoincorporates [I-125]-AZIPI and displays a low affinity for idazoxan, may not belong to the family of the I-2 imidazoline binding sites.