title: Pharmacological inhibition of AMP-deaminase in rat cardiac myocytes.
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 micro 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.
authors.affiliation: Department of Biochemistry, Medical University of Gdansk, Gdansk, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Borkowski
authors.forename: C
authors.initials: C
authors.lastname: Orlewska
authors.forename: E M
authors.initials: EM
authors.lastname: Slominska
authors.forename: A
authors.initials: A
authors.lastname: Yuen
authors.forename: M
authors.initials: M
authors.lastname: Lipinski
authors.forename: I
authors.initials: I
authors.lastname: Rybakowska
authors.forename: H
authors.initials: H
authors.lastname: Foks
authors.forename: K K
authors.initials: KK
authors.lastname: Kaletha
authors.forename: M H
authors.initials: MH
authors.lastname: Yacoub
authors.forename: R T
authors.initials: RT
authors.lastname: Smolenski
mesh_terms: D000659:AMP Deaminase / Q000037:antagonists & inhibitors*; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000138:chemical synthesis / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D007291:Inosine Monophosphate / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D051381:Rats
chemical_list: C421743:3-(2-(3-carboxy-4-bromo-5,6,7,8-tetrahydronaphthyl)ethyl)-3,6,7,8-tetrahydroimidazo(4,5-d)(1,3)diazepin-8-ol; D001381:Azepines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007291:Inosine Monophosphate; D000659:AMP Deaminase; D000241:Adenosine