RELATIONSHIP BETWEEN IMIDAZOLINE GUANIDINIUM RECEPTIVE SITES AND MONOAMINE-OXIDASE-A AND MONOAMINE-OXIDASE-B/

Imidazoline binding sites or imidazoline/guanidinium receptive sites ( IGRS) recognize bioactive endogenous substances and a variety of pharm acologically active compounds containing imidazoline or guanidinium mo ieties. The family of imidazoline binding proteins consists of multipl e membrane-associated proteins that differ in their tissue/subcellular localization, M(r) and ligand recognition properties. Two of the imid azoline binding proteins are identical to the mitochondrial enzyme mon oamine oxidase (MAO) A and B isoforms, which contain imidazoline bindi ng domains distinct from the enzyme active site. The relationship betw een the imidazoline binding proteins and monoamine oxidases was furthe r characterized in the present report using a covalent probe (2-[3-azi do-4[I-125]iodophenoxy]methyl imidazoline, [I-125]-AZIPI) to label the imidazoline binding proteins in different species and following trans ient expression of MAO-A and -B in COS 7 cells. Species homologues of MAO-A and -B in rat and human differ in their apparent molecular weigh t by approximate to 2000 Da. In rat and human liver [I-125]-AZIPI iden tified peptides with apparent molecular weights similar to those of th e species homologues of MAO. Peptides of M(r) approximate to 63,000 (M AO-A) and approximate to 59,000 (MAO-B) were also photolabeled in memb ranes prepared from COS-7 cells transfected with human cDNA clones enc oding MAO-A or -B. Additional experiments indicate that the imidazolin e binding domains on MAO-A and -B exhibit different ligand recognition properties. The covalent labeling of human liver MAO-B was more sensi tive than that of placenta MAO-A to inhibition by the imidazoline 2-(4 ,5-dihydroimidaz-2-yl)-quinoline (BU224). These data indicate that the A and B isoforms of MAO possess imidazoline binding domains that diff er in their ligand recognition properties. Allosteric regulation of th e activity of MAO via the imidazoline binding domains may be of signif icance in various disease states associated with elevated enzyme expre ssion or in which the enzyme is a therapeutic target. Copyright (C) 19 96 Elsevier Science Ltd.