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Biomedical subjects

C G Curtis

Publications and source records attributed to C G Curtis.

At least 55 records · Page 3Linked to original sources
PubMed1981

The enhanced biliary secretion of a taurine conjugate in the rat after intraduodenal administration of high doses of fenclozic acid.

1. The metabolic fate of [14C]fenclozic acid (ICI 54450) in rat was determined after intraduodenal administration at different doses. 2. Increasing the dose from 2 to 100 mg/kg resulted in a five-fold increase in drug-related material secreted in bile. 3. At a dose of 2 mg/kg the taurine conjugate was a relatively minor metabolite, whereas at 100 mg/kg this conjugate was the major metabolite in bile and urine. 4. Enhanced biliary secretion of the taurine conjugate in rats receiving multiple doses of fenclozic acid results in exposure of the intestinal cells to much greater concn. of drug-related metabolites.

Animals↗
PubMed1980

Kinetic measurements of the biliary excretion of metabolized compounds.

1. Rats received constant infusions of bromosulphophthalein or [carboxy-14C]cholic acid at a range of concentrations. 2. Kinetic parameters describing the biliary excretion of the compounds were determined. 3. The biliary excretion of both compounds could be described by the same kinetic parameters already calculated for phenolphthalein disulphate, which is excreted in the bile unchanged.

Animals↗
PubMed1980

A low-molecular-weight inhibitor of the neutral proteinase from rat intestinal smooth muscle.

1. Rat intestinal smooth muscle was shown to contain endogenous inhibitory activity towards the neutral trypsin-like muscle proteinase described previously [Beynon & Kay (1978) Biochem. J. 173, 291--298]. 2. Comtamination of the muscle tissue by mucosal, blood and pancreatic inhibitors was shown to be unlikely. 3. The inhibitory activity was resolved into high- and low-molecular-weight components. 4. The low-molecular-weight component was purified to homogeneity. It has a molecular weight of approx. 9000 and was stable over the pH range 3--11. 5. It inhibited the muscle proteinase competitively (Ki congruent to t microM), but had no effect on any of the other proteinases tested. 6. Leupeptin also inhibited the muscle proteinase competitively (Ki congruent to 0.3 microM), whereas the low-molecular weight proteins gastrin, glucagon and insulin B-chain had very little effect. 7. A role for a weakly binding inhibitor in modulating the influence of the neutral proteinase on intracellular protein degradation is considered.

Amino Acids↗
PubMed1980

Degradation of [3H]chondroitin 4-sulphate and re-utilization of the [3H]hexosamine component by the isolated perfused rat liver.

Radiolabelled chondroitin 4-sulphate was isolated after incubation of rat rib cartilage with N-acetyl-D-[6-3H]galactosamine. After proteolytic digestion of the tissue with either papain or trypsin the released [3H]chondroitin 4-sulphate was added to an isolated perfused rat liver system. Analysis of perfusate after several hours perfusion showed that radiolabelled amino sugars were secreted by the liver in a low-molecular-weight form and as components of glycoproteins.

Acetylgalactosamine↗
PubMed1978

Biliary excretion of cyclohexylphenyl 4-[35S]sulphate in the guinea pig.

The metabolic fate and mode of excretion of cyclohexylphenyl 4-[35S]sulphate were studied in the guinea pig. Up to 54.8% of the dose appeared in the bile, the majority as unchanged ester. Substantial amounts of hydroxylated cyclohexylphenyl 4-[35S]sulphate were also excreted in the bile together with minor amounts of the corresponding glucuronic acid conjugate. When isolated guinea-pig livers were perfused with cyclohexylphenyl 4-[35S]sulphate the biliary components were the same as those in the intact animal, although the relative concentration of the hydroxylated derivative was significantly greater. When the hydroxylated derivative was re-injected into guinea pigs it was excreted almost entirely unchanged in the bile. However, in the rat, it was excreted in the bile as a glucuronic acid conjugate. These findings are discussed in relation to studies carried out in the rat [Hearse, Powell, Olavesen & Dodgson (1969) Biochem. Pharmacol. 18, 181--195] and to differences in enzyme activities in rat and guinea-pig liver. The results are also discussed in terms of the molecular-weight threshold for the excretion of anions in guinea-pig bile.

Animals↗
PubMed1978

Studies on the fate of pulmonary surfactant in the lung.

1. Radioactively labelled pulmonary surfactant was prepared in an isolated perfused lung system provided with [14C]hexadecanoate. 2. After intratracheal administration of pulmonary surfactant radioactively labelled components were rapidly distributed into different lung fractions, including macrophages (free cells), but most of the radioactive label was accumulated by the lung tissue. 3. Alveolar macrophages, maintained in a variety of culture media in the presence and absence of mineral particles, incorporated a low percentage (11%) of radioactively labelled components when incubated with the surfactant, although evolution of labelled CO2 (6% of the original total activity) suggested that some breakdown of the components had taken place. 4. In similar cultures little intracellular accumulation or extracellular release of non-esterified fatty acids was demonstrated, indicating minimal catabolism of the high-molecular-weight lipid components of surfactant (particularly phosphatidylcholine). 5. However, experiments in vitro designed to simulate the lysosomal degradation of endocytosed surfactant indicated that the macrophage had enzymes capable of releasing non-esterified fatty acids, particularly hexadecanoate, from the lipoprotein complex. 6. It is argued that lung cells, other than alveolar macrophages, may also have a role in surfactant turnover.

Animals↗
PubMed1978

Utilization by the isolated perfused rat liver of N-acetyl-D-[1-14C]galactosamine and N-[3H]acetyl-D-galactosamine for the biosynthesis of glycoproteins.

The isolated perfused rat liver system has been used to monitor the utilization of N-[3H]acetyl-D-galactosamine and N-acetyl-D-[1-14C]galactosamine for the biosynthesis of radiolabelled glycoproteins, which are subsequently secreted into the plasma. Both radiolabels appear in a number of different glycoproteins, predominantly as sialic acid and N-acetylglucosamine. The ratio of labelled sialic acid to labelled N-acetylglucosamine varies for different glycoproteins, but the bulk of N-acetyl-D-galactosamine is incorporated without deacetylation.

Acetylgalactosamine↗
PubMed1978

Ca2+-related regulatory function of fibrinogen.

Fibrinogen displays a regulation of considerable physiological significance by lowering the Ca2+ requirement for the conversion of the fibrin-stabilizing factor (Factor XIII) zymogen to the range of concentrations of this ion found in plasma. Fibrinogen modulates both Ca2+-dependent steps in the complex process of zymogen activation, involving the heterologous dissociation of subunits of the thrombin-modified zymogen (Factor XIII') species : formula: (see text) and the unmasking of iodoacetamide titratable sites during generation of transamidating activity : formula: (see text). It is interesting that a thrombin-independent pathway of zymogen activation : formula: (see text), which we found to operate at Ca2+ concentrations above 50 mM, is not affected by the presence of fibrinogen. Regulation by fibrinogen thus appears to be specific for controlling only the physiological pathway of zymogen conversion.

Binding Sites↗
PubMed1978

The distribution and excretion of non-biodegradable anionic surfactants.

1. The metabolism of potassium 10-undecenyl [35S]sulphate and potassium 10-phenyldecyl [35S]sulphate was investigated in the rat. 2. The major route for elimination of radioactivity following potassium 10-undecenyl [35S]sulphate administration was urinary. With 10-phenyldecyl [35S]sulphate the major route of elimination was biliary. 3. Whole-body radioautography and isolated liver perfusion experiments established that both esters were concentrated in the liver, the major organ of metabolism. 4. Neither surfactant was degraded to short-chain anionic derivatives but both compounds were extensively metabolized.

Animals↗
PubMed1977

Biliary excretion of some anionic derivatives of diethylstilboestrol and phenolphthalein in the guinea pig.

The metabolic fates and modes of excretion of diethylstilboestrol mono[35S]sulphate and diethylstilboestrol di[35S]sulphate were studied in the guinea pig. Comparative studies were also made with [G-3H]diethylstilboestrol and phenolphthalein di[35S]sulphate. Diethylstiboesterol di[35S]sulphate was extensively eliminated in the bile unchanged. After administration of diethylstilboestrol mono[35S]sulphate, extensive biliary elimination of radioactivity was also recorded. Radioactive components were identified as diethylstilboestrol disulphate, diethylstilboestrol monosulphate monoglucuronide and unchanged diethylstilboestrol monosulphate. When [G-3H]diethylstilboestrol was administered, 3H-labelled diethylstilboestrol monoglucuronide, diethylstilboestrol monosulphate monoglucuronide and diethylstilboestrol disulphate appeared in the bile. Phenolphthalein di[35S]sulphate was excreted unchanged in bile. These findings are discussed in relation to studies carried out in the rat [Barford, Olavesen, Curtis & Powell (1977) Biochem. J. 164, 423--430] and species differences are related to differences in enzyme activities in rat and guinea-pig liver.

Animals↗
PubMed1977

The catabolism of intravenously injected heparan N-[35S] sulphate in the rat.

The metabolic fate of heparan N-[(35)S]sulphate was studied in rats. Heparan sulphate was obtained from either bovine aorta or lung and labelled with (35)S by desulphation and subsequent resulphation in vitro. Experiments in which heparan N-[(35)S]sulphate was administered intravenously to either free-range or wholly anaesthetized rats with ureter cannulae established that substantial desulphation occurs in vivo, with elimination of inorganic [(35)S]sulphate in urine. Oligosaccharides labelled with (35)S, possible intermediates in heparan sulphate degradation, could not be detected in urine or blood. The general distribution of radioactivity after administration of heparan N-[(35)S]sulphate, as demonstrated by whole-body radioautography, suggested that desulphation was not restricted to one organ in particular. Support for this view was obtained in experiments in which heparan N-[(35)S]sulphate was administered to animals after the removal of kidneys, liver, spleen, pancreas or gastrointestinal tract. In all cases inorganic [(35)S]sulphate was still produced. The ability of rats of desulphate heparan N-[(35)S]sulphate was progressively impaired by increasing concentrations of heparin administered simultaneously. It was concluded that heparan sulphate is metabolized at a number of sites in the body by a sequence of degradative events leading to the formation of inorganic sulphate. It is also concluded that at least some of these events are common to heparan sulphate and heparin.

Animals↗
PubMed1977

Metabolic fates of diethylstilboestrol sulphates in the rat.

The metabolic fates and modes of excretion of diethylstilboestrol mono[35S]sulphate and diethylstilboestrol di[35S]sulphate were studied in the rat. Both of the esters were desulphated to some extent in vivo. In addition, significant amounts of radioactivity appeared in the bile as diethylstilboestrol mono[35S]sulphate monoglucuronide. The percentage of the dose appearing in bile as the diconjugate was substantially greater in experiments with diethylstilboestrol mono[35S]sulphate than with diethylstilboestrol di[35S]sulphate. Whole-body radioautography and studies with isolated perfused liver confirmed the liver as the major metabolic organ for both esters. When the metabolite diethylstilboestrol mono[35S]sulphate monoglucuronide isolated from the bile was reinjected, it was excreted in the bile unchanged. Studies in vitro demonstrated that both esters were substrates for arylsulphatase C with Km values in the range 52-76 micrometer. The metabolic fates and modes of excretion of the esters are discussed in relation to the enzyme complement of rat liver.

Animals↗