3-Isobutylmethylxanthine Inhibits Hepatic Urea Synthesis

Abstract

We previously showed that agmatine stimulated hepatic ureagenesis. In this study, we sought to determine whether the action of agmatine is mediated via cAMP signaling. A pilot experiment demonstrated that the phosphodiesterase inhibitor

Effects of a glucokinase activator on hepatic intermediary metabolism: study with 13C-isotopomer-based metabolomics

“…In each perfusion, samples were taken from the influent and effluent media for measurement of 13 CO 2 release, enzymatic assays, GC (gas chromatography)-MS or LC (liquid chromatography)-MS analyses as indicated [9,10]. At the end of perfusion the liver was freeze-clamped with aluminum tongs pre-cooled in liquid N 2 .…”

“…Briefly, an aliquot (500 μ l) of effluent, liver or hepatocyte extracts was purified by passage through an AG-1 column (Cl − : 100–200 mesh; 0.5 cm×2.5 cm) for separation of organic acids and glutamate and aspartate residues or by passage through an AG-50 column (H + : 100–200 mesh) for separation of alanine, serine, glycine and glutamine residues and urea. Then, samples were converted into the t-butyldimethylsilyl derivatives [9,10]. Isotopic enrichment in [ 13 C]alanine isotopomers was monitored using ions at m / z 260, 261, 262 and 263 for M0, M1, M2 or M3 (containing one to three 13 C atoms above M0, the natural abundance) respectively.…”

“…CH 3 -CH 2 -CH 2 -CH 2 -OH). After the initial measurement of 13 C enrichment in NAG isotopomers, the samples were spiked with a known amount of NAG for determination of the NAG concentration by isotope dilution [10]. The production of 15 N-labelled urea isotopomers (containing one or two 15 N atoms) from 15 NH 4 Cl and its output in the perfusate were determined as described previously [16].…”

“…in the 13 C-NMR spectra. Data acquisition and calculation of percentage 13 C enrichment in various glutamate carbons were performed as described in [10,17]. P i or compounds containing phosphate were identified and their levels were measured relative to the resonance of methylene diphosphonate (16.7 p.p.m.)…”

High-throughput respirometric assay identifies predictive toxicophore of mitochondrial injury

“…IBMX is a competitive phosphodiesterase inhibitor and an adenosine antagonist 39,40 . Nissim et al, demonstrated that IBMX exposure inhibited the mitochondrial respiratory chain and reduced OCR during liver perfusion of rats 41 . 1,3 dimethyl-8-phenyltheophylline is a selective A 1 adenosine receptor antagonist; however, there are no known effects of this compound on mitochondrial function 42 .…”