Imidazoline Binding Domains on MAO-B: Localization and Accessibility

Authors


Address for correspondence: Stephen M. Lanier, Ph.D., Department of Pharmacology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425. Phone, 803 792–2574; fax, 803 792–2475; e-mail, laniersm@musc.edu

Abstract

ABSTRACT: Various imidazoline and guanidinium derivatives elicit diverse cellular responses in both peripheral tissues and the central nervous system that are often difficult to attribute to known receptor signaling systems. Such molecules also exhibit high affinity for membrane proteins (imidazoline binding sites) that are distinct from receptors for known hormones and recognize endogenous bioactive substance(s) that mimic some of the effects of these compounds. These observations suggest a previously uncharacterized cell signaling system. However, limited information on the identity and functionality of this family of imidazoline binding sites has hampered the full understanding of this system. Unexpectedly and of particular significance, recent data indicate that two members of the family of imidazoline binding proteins are identical to the A and B isoforms of monoamine oxidase (MAO). The imidazoline binding domain on MAO is distinct from the enzyme active site that recognizes the mechanism-based inhibitors such as pargyline and deprenyl and is not equally accessible in all tissues.

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