Abstract
The product of agmatine oxidation catalyzed by Pisum sativum L. copper amine oxidase has been identified by means of one- and two-dimensional (1)H-NMR spectroscopy to be N-amidino-2-hydroxypyrrolidine. This compound inhibits competitively rat nitric oxide synthase type I and type II (NOS-I and NOS-II, respectively) and bovine trypsin (trypsin) activity, values of Ki being (1.1 +/- 0.1) x 10(-5) m (at pH 7.5 and 37.0 degrees C), (2.1 +/- 0.1) x 10(-5) m (at pH 7.5 and 37.0 degrees C), and (8.9 +/- 0.4) x 10(-5) m (at pH 6.8 and 21.0 degrees C), respectively. Remarkably, the affinity of N-amidino-2-hydroxypyrrolidine for NOS-I, NOS-II and trypsin is significantly higher than that observed for agmatine and clonidine binding. Furthermore, N-amidino-2-hydroxypyrrolidine and agmatine are more efficient than clonidine in displacing [(3)H]clonidine (= 1.0 x 10(-8) m) from specific binding sites in heart rat membranes, values of IC50 being (1.3 +/- 0.4) x 10(-9) m and (2.2 +/- 0.4) x 10(-8) m, respectively (at pH 7.4 and 37.0 degrees C).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Agmatine / chemistry
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Agmatine / metabolism*
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Agmatine / pharmacology
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Amine Oxidase (Copper-Containing) / metabolism*
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Animals
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Binding, Competitive
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Clonidine / metabolism
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Clonidine / pharmacology
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Humans
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Imidazoline Receptors
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Inhibitory Concentration 50
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Magnetic Resonance Spectroscopy
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Male
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Membranes / drug effects
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Membranes / metabolism
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Models, Molecular
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / chemistry
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Nitric Oxide Synthase / metabolism
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Nitric Oxide Synthase Type I
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Nitric Oxide Synthase Type II
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Oxidation-Reduction
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Pisum sativum / enzymology
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Pyrrolidines / chemistry
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Pyrrolidines / metabolism*
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Rats
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Rats, Wistar
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Receptors, Drug / metabolism
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Trypsin / chemistry
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Trypsin / drug effects
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Trypsin / metabolism
Substances
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Imidazoline Receptors
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N-amidino-2-hydroxypyrrolidine
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Pyrrolidines
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Receptors, Drug
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imidazoline I1 receptors
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Agmatine
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NOS1 protein, human
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NOS2 protein, human
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type I
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Nitric Oxide Synthase Type II
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Nos1 protein, rat
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Nos2 protein, rat
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Amine Oxidase (Copper-Containing)
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Trypsin
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Clonidine