TY - JOUR T1 - Analysis of the Pharmacological and Molecular Heterogeneity of I<sub>2</sub>-Imidazoline-Binding Proteins using Monoamine Oxidase-Deficient Mouse Models JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1085 LP - 1090 DO - 10.1124/mol.58.5.1085 VL - 58 IS - 5 AU - Anne Remaury AU - Rita Raddatz AU - Catherine Ordener AU - Sandra Savic AU - Jean C. Shih AU - Kevin Chen AU - Isabelle Seif AU - Edward De Maeyer AU - Stephen M. Lanier AU - Angelo Parini Y1 - 2000/11/01 UR - http://molpharm.aspetjournals.org/content/58/5/1085.abstract N2 - The I2 subgroup of imidazoline-binding sites was identified as monoamine oxidases (MAOs), but it is unclear whether there are I2-binding sites located on proteins distinct from MAOs. To address this issue, we characterized I2-binding proteins in liver and brain of wild-type and MAO A- and MAO B-deficient mice. I2-binding sites were identified using [3H]idazoxan and the photoaffinity adduct 2-[3-azido-4-[125I]iodophenoxyl]methylimidazoline ([125I]AZIPI). [3H]Idazoxan labeled binding sites with ligand recognition properties typical of I2sites in both brain and liver of wild-type mice. High-affinity, specific [3H]idazoxan binding were not altered in MAO A knockout (KO) mice. In contrast, [3H]idazoxan binding was completely abolished in both liver and brain of MAO B KO mice. In wild-type mice, [125I]AZIPI photolabeled three proteins with apparent molecular masses of ∼28 (liver), ∼61 (brain), and ∼55 kDa (liver and brain). The photolabeling of each protein was blocked by the imidazoline cirazoline (10 μM). Photolabeling of the ∼61- and ∼55-kDa proteins was not observed in MAO A and B KO mice, respectively. In contrast, photolabeling of the liver ∼28-kDa protein was still observed in MAO-deficient mice, indicating that this protein is unrelated to MAOs. These data indicate that I2 imidazoline-binding sites identified by [3H]idazoxan reside solely on MAO B. The binding sites on MAO A and the liver ∼28-kDa protein may represent additional subtypes of the family of the imidazoline-binding sites. ER -