Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

A group of structurally-related compounds known to interact with imidazoline binding proteins (also called imidazoline receptors) have been reported to inhibit MAO activity. The involvement of imidazoline binding proteins in the biological activities of compounds such as idazoxan, cirazoline, clonidine and amiloride remains a subject of great debate. MAO-A and -B were identified as members of the family of imidazoline binding proteins by the photoaffinity probe 2-[3-azido-4[125I]iodophenoxy]methyl imidazoline. The imidazoline binding domain (IBD) on MAO-B was localized to amino acids K149 - M222, a domain of the enzyme that is distinct from the proposed site of interaction with classical MAO inhibitors. Interestingly, the IBD appears to be accessible on a small subpopulation of MAO-B and that accessibility is tissue dependent (liver > adipocyte ~ kidney > brain > platelet). The source and significance of this heterogeneity within MAO-B molecules remains unclear. Previously reported mutational studies implicate the IBD in the regulation of MAO function suggesting that this binding site may be a novel target for enzyme regulation. Although imidazoline/ guanidinium compounds inhibited MAO-B activity at very high concentrations, isolation of the subpopulation of MAO-B recognizing these compounds is necessary to determine the role of the IBD in enzyme function.

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Presentation Number SAraddatz0472
Keywords: monoamine oxidase, imidazoline, guanidinium, MAO inhibitor, idazoxan