RT Journal Article SR Electronic T1 Analysis of the Pharmacological and Molecular Heterogeneity of I2-Imidazoline-Binding Proteins using Monoamine Oxidase-Deficient Mouse Models JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1085 OP 1090 DO 10.1124/mol.58.5.1085 VO 58 IS 5 A1 Anne Remaury A1 Rita Raddatz A1 Catherine Ordener A1 Sandra Savic A1 Jean C. Shih A1 Kevin Chen A1 Isabelle Seif A1 Edward De Maeyer A1 Stephen M. Lanier A1 Angelo Parini YR 2000 UL http://molpharm.aspetjournals.org/content/58/5/1085.abstract AB 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.