Pharmacological Inhibition of AMP-Deaminase in Rat Cardiac Myocytes |
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| Authors: | T Borkowski C Orlewska E M Slominska A Yuen M Lipinski I Rybakowska |
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| Institution: | 1. Department of Biochemistry , Medical University of Gdansk , Gdansk, Poland;2. Department of Organic Chemistry , Medical University of Gdansk , Gdansk, Poland;3. Heart Science Centre , Imperial College London , London, United Kingdom;4. Department of Pharmaceutical Biochemistry , Medical University of Gdansk , Gdansk, Poland;5. Department of Clinical Biochemistry and Physiology , Medical University of Gdansk , Gdansk, Poland |
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| Abstract: | Because mutation of AMP deaminase 1 gene leading to reduced AMP deaminase activity may result in protection of cardiac function in patients with heart disease, inhibitors of AMP deaminase (AMPD) may have therapeutic applications. This study evaluated the effect of a specific inhibitor of AMP deaminase 3-2-(3-carboxy-4-bromo-5,6,7,8-tetrahydronaphthyl)ethyl]-3,6,7,8-tetrahydroimidazo 4,5-d]1,3]diazepin-8-ol (AMPDI) on the isolated human enzyme and on nucleotide catabolism in rat cardiomyocytes. AMPDI effectively inhibited isolated human AMPD with an IC 50 = 0.5 μ M. AMPDI was much less effective with isolated cardiomyocytes (IC 50 = 0.5 mM). AMPDI is a very effective inhibitor of AMPD that despite lower efficiency in the cell system examined could be useful for in vivo studies. |
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| Keywords: | AMP deaminase AMP deaminase inhibitor cardiomyocytes rat |
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