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J Capdevila

Publications and source records attributed to J Capdevila.

At least 37 records · Page 2Linked to original sources
PubMed1985

Novel glutathione conjugates formed from epoxyeicosatrienoic acids (EETs).

The catalysis of glutathione (GSH) conjugation to epoxyeicosatrienoic acids (EETs) by various purified isozymes of glutathione S-transferase was studied. A GSH conjugate of 14,15-EET was isolated by HPLC and TLC; this metabolite contained one molecule of EET and one molecule of GSH. Fast atom bombardment mass spectrometry of the isolated metabolite confirmed the structure as a GSH conjugate of 14,15-EET. Studies designed to determine the isozyme specificity of this reaction demonstrated that two isozymes, 3-3, and 5-5, efficiently catalyzed this conjugation reaction. The Km values for 14,15-EET were approximately 10 microM and the Vmax values ranged from 25 to 60 nmol conjugate formed min-1 mg-1 purified transferase 3-3 and 5-5. The 5,6-, 8,9-, and 11,12-EETs were also substrates for the reaction, albeit at lower rates. These results demonstrate that the EETs can serve as substrates for the cytosolic glutathione S-transferases.

8,11,14-Eicosatrienoic Acid↗
PubMed1985

Involvement of eicosanoids in release of oxytocin and vasopressin from the neural lobe of the rat pituitary.

Arachidonic acid (AA) is oxidized via three pathways which result in several series of distinct metabolites. Cyclooxygenase produces prostaglandins (PGs), prostacyclins, and thromboxanes. Lipoxygenase produces hydroperoxy/hydroxyeicosatetraenoic acids (HPETE/HETEs) and leukotrienes. Epoxygenase, a recently uncovered pathway, results in epoxyeicosatrienoic acids (EETs). Based on reverse phase HPLC product analysis, this study establishes that all three pathways of AA metabolism are present in microsomal incubates of the neural lobe of the pituitary gland. Addition of PGE2 to incubated fragments of neural lobes of the rat pituitary stimulates secretion of both arginine vasopressin (AVP) and oxytocin in vitro. Inclusion of 5-HETE and 12-HETE in the incubation medium stimulates marginal release of AVP and oxytocin by 12-HETE only. The magnitude of AVP and oxytocin secretion stimulated by the epoxygenase metabolites 8,9-, 11,12-, and 14,15-EET is equal to that caused by PGE2. Maximal stimulation of secretion (3- to 4-fold) requires an EET concentration 10-15 times greater than that of PGE2. In contrast, 5,6-EET is inactive. These data suggest that oxygenated products of AA play a role in AVP and oxytocin secretion. Although PGs appear to be the dominant arachidonate metabolites involved in the release of AVP and oxytocin, the EETs probably have a contributing role.

Animals↗
PubMed1979

The metabolic activation of benzo(a)pyrene and 9-hydroxybenzo(a)pyrene by liver microsomal fractions.

A rat liver microsome-mediated bacterial mutagenicity test showed 9-hyroxybenzo(a)pyrene to be significantly more effective as a pre-mutagen than benzo(a)pyrene. Experiments measuring the ability of these compounds to be metabolically activated to moieties that alkylate exogenous DNA demonstrated that 9-hydroxybenzo(a)pyrene was almost six times more effective than benzo(a)pyrene itself. Addition of trichloropropene-2,3-oxide to the reaction mixture enhanced the mutagenicity and DNA alkylation by benzo(a)pyrene but had little or no effect on the 9-hydroxybenzo(a)pyrene-mediated mutagenicity and alkylation. On the other hand, 7,8-benzoflavone inhibited the microsome-mediated mutagenicity and DNA alkylating activity of both hydrocarbons.

Alkylation↗
PubMed1979

Diagnostic value of leucocytic acid-phosphatase isoenzymes in determining cytological types of non-lymphoid acute leukaemias.

The normal isoenzymatic pattern of leucocytic acid-phosphatase based on the study of 150 haematologically normal individuals is reported. The different pathologic patterns of the leucocytic acid-phosphatase isoenzymes occurring in non-lymphoblastic acute leukaemias are presented and correlated with the subdivisions of acute leukaemias established by the French-American-British (FAB) Co-operative Group. This study is considered to be especially useful in identifying pure acute monocytic leukaemias corresponding to subtype M5 of the FAB as well as acute erythraemias with unusual cytological and cytochemical features.

Acid Phosphatase↗
PubMed1975

The metabolism of benzo(alpha)pyrene in isolated rat liver cells.

Isolated rat liver cells catalyze the metabolism of benzo(alpha)pyrene (BP) with the resulting formation of phenols, dihydrodiols, and conjugates. The rate of the primary oxidative step in the process was similar to that catalyzed by isolated rat liver microsomes in the presence of a reduced nicotinamide adenine dinucleotide phosphate-generating system and responded similarly to various inhibitors, including 2-diethylaminoethyl-2,2-diphenylvalerate, metyrapone, alpha-naphthoflavone, and hexobarbital. The level of cytoplasmic, reduced nicotinamide adenine dinucleotide phosphate was not rate limiting in liver cells isolated from either fed or fasted animals. The conjugates and dihydrodiols formed were readily excreted, whereas low concentrations of phenols accumulated intracellularly. The pattern of metabolites of BP was the same in isolated rat liver cells and in the isolated perfused rat liver. 3-Methylcholanthrene treatment of the rats caused a marked increase in cellular BP metabolism as well as in cytochrome P-450 concentration. The induced hemoprotein revealed characteristics similar to those previously established with isolated liver microsomes, i.e., increase in high-spin form, enhanced affinity for BP as revealed by a lower Michaelis constant, and sensitivity to the inhibitory action of alpha-naphthoflavone. After 3-methylcholanthrene treatment, phenols and dehydrodiols constituted a larger percentage of the total metabolites, indicating a more pronounced stimulation of the oxidative than of the conjugative step of BP metabolism by induction, and the dihydrodiols now tended to accumulate intracellularly.

Animals↗
PubMed1975

Characterization of a rat lung microsomal fraction obtained by sepharose 2B ultrafiltration.

A new procedure for obtaining rat lung microsomes essentially free of interfering hemoproteins has been developed. The method includes Sepharose 2B column chromatography of the 12,000 X g supernatant of lung homogenates, followed by ultracentrifugation of the material eluted in the void volume. Microsomes isolated in this manner contain specific levels of cytochromes b5 and P-450 and of NADPH-cytochrome c reductase that are among the highest ever reported for a rat lung microsomal fraction. After treatment of rats with 3-methylcholanthrene, the specific content of cytochrome P-450 in lung microsomes is doubled and that of cytochrome b5 increases 1.5 times. Several spectral differences between hepatic and lung microsomal cytochrome P-450 are apparent. In lung microsomes, the maximum of the reduced CO-bound cytochrome complex in a difference spectrum is at 453 nm for the noninduced hemoprotein and shifts to 451 nm after 3-methylcholanthrene induction. In contrast, no significant change in the ethylisocyanide difference spectra of reduced microsomes is obtained after induction; moreover, the spectra obtained with induced and noninduced cytochrome P-450 are similar to the one shown by hepatic microsomes from polycyclic hydrocarbon-treated rats. Furthermore, spectrophotometric studies on n-octylamine binding to control and induced lung cytochrome P-450 yielded results different from those previously obtained with rabbit liver microsomes. It is concluded that the cytochrome P-450 present in rat lung microsomes before and after 3-methylcholanthrene treatment of the animals is distinctly different from the liver hemoprotein.

Animals↗