scholarly journals Species differences in the metabolism of sulphadimethoxine

1968 ◽  
Vol 109 (5) ◽  
pp. 851-856 ◽  
Author(s):  
J W Bridges ◽  
M. R. Kibby ◽  
S R Walker ◽  
R T Williams
Keyword(s):  
Guinea Pig ◽  
Species Differences ◽  
Glucuronic Acid ◽  
Acetyl Derivative ◽  
Unchanged Drug ◽  
Rat Urine ◽  
Monkey Liver ◽  
Liver Homogenates ◽  
Rat Bile ◽  
Do So

1. The fate of sulphadimethoxine (2,4-dimethoxy-6-sulphanilamidopyrimidine) was studied in man, rhesus monkey, dog, rat, guinea pig and rabbit. 2. About 20–46% of the dose (0·1g./kg.) of the drug is excreted in the urine in 24hr. in these species, except the rat, in which only 13% is excreted. 3. In man and the monkey sulphadimethoxine N1-glucuronide is the major metabolite in the urine. In the rabbit and guinea pig N4-acetylsulphadimethoxine is the main metabolite. In the dog the drug is excreted mainly unchanged. In the rat equal amounts of the unchanged drug and its N4-acetyl derivative are the main products. 4. Small amounts of sulphadimethoxine N4-glucuronide are found in the urine of all the species. Sulphadimethoxine N1-glucuronide occurs in small amounts in the urine of rat, dog and guinea pig; none is found in rabbit urine. 5. Sulphadimethoxine N4-sulphate was synthesized and found to occur in small amounts in rat urine. 6. Monkey liver homogenates fortified with UDP-glucuronic acid are able to synthesize sulphadimethoxine N1-glucuronide with the drug as substrate. Rat liver has also this ability to a slight extent, but rabbit liver is unable to do so. 7. Sulphadimethoxine N4-glucuronide is formed spontaneously when the drug is added to human urine. 8. The biliary excretion of the drug and its metabolites was examined in rats. The drug is excreted in rat bile mainly as the N1-glucuronide. The N1- and N4-glucuronides administered as such are extensively excreted in the bile by rats.

scholarly journals Species differences in the metabolism and excretion of sulphasomidine and sulphamethomidine

1969 ◽  
Vol 111 (2) ◽  
pp. 173-179 ◽  
Author(s):  
J W Bridges ◽  
S R Walker ◽  
R T Williams
Keyword(s):  
Partition Coefficients ◽  
Species Differences ◽  
Species Difference ◽  
Acetyl Derivative ◽  
The Other ◽  
Main Metabolite ◽  
Monkey Liver ◽  
Liver Homogenates

1. The excretion of 2,4-dimethyl-6-sulphanilamidopyrimidine (sulphasomidine; Elkosin) and 4-methoxy-2-methyl-6-sulphanilamidopyrimidine (sulphamethomidine) given orally was examined in man, rhesus monkey, rabbit and rat. 2. About 70% of sulphasomidine (0·1g./kg.) is excreted mainly unchanged in the urine by these species in 24hr.; less than 15% of the dose is acetylated and there is no marked species difference in the fate of this drug. 3. Sulphamethomidine is excreted more slowly than sulphasomidine, and in the rat, rabbit and monkey the main metabolite is the N4-acetyl derivative. In man, only 20–30% of the dose is excreted in 24hr. and nearly 70% of this is sulphamethomidine N1-glucuronide, which is also excreted by the monkey but not by the rat or rabbit. There is therefore a marked species difference in the metabolism of sulphamethomidine. 4. Sulphamethomidine N1-glucuronide was synthesized and shown to be identical with the glucuronide isolated from monkey urine. 5. Sulphasomidine, sulphamethomidine and sulphadimethoxine (2,4-dimethoxy-6-sulphanilamidopyrimidine) were acetylated by rabbit or monkey liver homogenates. Although sulphasomidine is poorly acetylated in vivo, it is acetylated in vitro at rates comparable with those of the other two drugs. 6. The solubilities, partition coefficients and plasma-protein-binding of the drugs were measured. 7. The results are discussed.

scholarly journals The biosynthesis of tyramine glucuronide by liver microsomal fractions

1977 ◽  
Vol 164 (3) ◽  
pp. 529-531 ◽  
Author(s):  
K P Wong
Keyword(s):  
Monoamine Oxidase ◽  
Guinea Pig ◽  
Glucuronic Acid ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Freezing And Thawing ◽  
Monkey Liver ◽  
Specific Activities ◽  
Low Activity

Labelled tyramine glucuronide was synthesized in vitro from UDP-[14C]glucuronic acid, [14C]tyramine or [3H]tyramine. The glucuronidation was carried out at pH9.2 in the presence of a monoamine oxidase inhibitor, trans-2-phenylcyclopropylamine. The Km values for tyramine were 69 and 125 micrometer and those for UDP-glucuronic acid were 260 and 290 micrometer respectively for guinea-pig and rat liver microsomal preparatons. The specific activities of microsomal glucuronyltransferase measured in fresh hepatic preparations of guinea pig, mouse and rat were respectively 601, 251 and 235 pmol of [14C]tyramine glucuronide/min per mg of protein. Increase in activity ranged from 2- to 6-fold in preparations which were frozen and thawed once and 5.4- to 10-fold when the freezing and thawing was repeated. Rabbit liver has very low activity, and monkey liver and intestine were completely devoid of this conjugating capacity.

scholarly journals Metabolism of [14C]methamphetamine in man, the guinea pig and the rat

1972 ◽  
Vol 129 (1) ◽  
pp. 11-22 ◽  
Author(s):  
J. Caldwell ◽  
L. G. Dring ◽  
R. T. Williams
Keyword(s):  
Guinea Pig ◽  
Benzoic Acid ◽  
Methyl Ketone ◽  
Species Differences ◽  
Human Subjects ◽  
Main Reaction ◽  
Unchanged Drug ◽  
Aromatic Hydroxylation ◽  
Dose Dependent ◽  
Acid Labile

1. The metabolites of (±)-2-methylamino-1-phenyl[1-14C]propane ([14C]methamphetamine) in urine were examined in man, rat and guinea pig. 2. In two male human subjects receiving the drug orally (20mg per person) about 90% of the14C was excreted in the urine in 4 days. The urine of the first day was examined for metabolites, and the main metabolites were the unchanged drug (22% of the dose) and 4-hydroxymethamphetamine (15%). Minor metabolites were hippuric acid, norephedrine, 4-hydroxyamphetamine, 4-hydroxynorephedrine and an acid-labile precursor of benzyl methyl ketone. 3. In the rat some 82% of the dose of14C (45mg/kg) was excreted in the urine and 2–3% in the faeces in 3–4 days. In 2 days the main metabolites in the urine were 4-hydroxymethamphetamine (31% of dose), 4-hydroxynorephedrine (16%) and unchanged drug (11%). Minor metabolites were amphetamine, 4-hydroxyamphetamine and benzoic acid. 4. The guinea pig was injected intraperitoneally with the drug at two doses, 10 and 45mg/kg. In both cases nearly 90% of the14C was excreted, mainly in the urine after the lower dose, but in the urine (69%) and faeces (18%) after the higher dose. The main metabolites in the guinea pig were benzoic acid and its conjugates. Minor metabolites were unchanged drug, amphetamine, norephedrine, an acid-labile precursor of benzyl methyl ketone and an unknown weakly acidic metabolite. The output of norephedrine was dose-dependent, being about 19% on the higher dose and about 1% on the lower dose. 5. Marked species differences in the metabolism of methamphetamine were observed. The main reaction in the rat was aromatic hydroxylation, in the guinea pig demethylation and deamination, whereas in man much of the drug, possibly one-half, was excreted unchanged.

Die Bedeutung der Homogenisationsart und -intensität für die Größe und Konstanz der Sauerstoffaufnahme von Meerschweinchen-Leberhomogenat / The Influence of Mode and Intensity of Homogenization on the Absolute Value and Stability of Oxygen Consumption of Guinea Pig Liver Homogenates

1977 ◽  
Vol 32 (11-12) ◽  
pp. 908-912 ◽  
Author(s):  
H. J. Schmidt ◽  
U. Schaum ◽  
J. P. Pichotka
Keyword(s):  
Oxygen Uptake ◽  
Guinea Pig ◽  
Measuring Time ◽  
Pig Liver ◽  
Absolute Value ◽  
Modified Method ◽  
Simultaneous Measurements ◽  
Liver Homogenates ◽  
The Absolute ◽  
Guinea Pig Liver

Abstract The influence of five different methods of homogenisation (1. The method according to Potter and Elvehjem, 2. A modification of this method called Potter S, 3. The method of Dounce, 4. Homogenisation by hypersonic waves and 5. Coarce-grained homogenisation with the “Mikro-fleischwolf”) on the absolute value and stability of oxygen uptake of guinea pig liver homogenates has been investigated in simultaneous measurements. All homogenates showed a characteristic fall of oxygen uptake during measuring time (3 hours). The modified method according to Potter and Elvehjem called Potter S showed reproducible results without any influence by homogenisation intensity.

scholarly journals COMPARISONS OF THE OXIDATION OF C19-HYDROXYSTEROIDS BY GUINEA PIG LIVER HOMOGENATES

1957 ◽  
Vol 224 (2) ◽  
pp. 811-818
Author(s):  
Charles D. Kochakian ◽  
Betty R. Carroll ◽  
Barbara Uhri
Keyword(s):  
Guinea Pig ◽  
Pig Liver ◽  
Liver Homogenates ◽  
Guinea Pig Liver

SPECIES DIFFERENCES IN THE DEOXYRIBONUCLEIC AND RIBONUCLEIC ACID CONTENTS OF LIVERS OF NON-PREGNANT AND PREGNANT MICE, GUINEA-PIGS AND CATS

1953 ◽  
Vol 9 (1) ◽  
pp. 45-51 ◽  
Author(s):  
ROSA M. CAMPBELL ◽  
H. W. KOSTERLITZ
Keyword(s):  
Guinea Pig ◽  
Protein Content ◽  
Liver Cell ◽  
Ribonucleic Acid ◽  
Guinea Pigs ◽  
Deoxyribonucleic Acid ◽  
Species Differences ◽  
Liver Cells ◽  
Maternal Liver ◽  
Pregnant Mice

1. The protein content of liver cells is almost independent of the size of the animal (mice, cats and previous results on rats, Campbell & Kosterlitz [1949]), and varies with the amount of protein eaten. 2. As has already been shown for rats, the ribonucleic acid ('RNA') content of the liver cells of non-pregnant mice, guinea-pigs and cats varies directly with the protein content of the cells. For a given protein content the mouse and rat have more RNA than the guinea-pig and cat. 3. During pregnancy there is a rise of the deoxyribonucleic acid ('DNA') content of the livers and in the protein content of the liver cells of mice (and rats), but not of guinea-pigs. 4. An excess of RNA over that predicted from the protein content of the liver cell has previously been found for the rat during pregnancy, and ascribed to the action of a placental factor on the maternal liver. A similar excess of RNA has now been observed in the mouse and, to a less extent, in the guinea-pig. It appears to be absent in the cat. 5. Possible causes of some of these species differences are considered.

scholarly journals Enzymic transfer of glucose and xylose from uridine diphosphate glucose and uridine diphosphate xylose to bilirubin by untreated and digitonin-activated preparations from rat liver

1972 ◽  
Vol 129 (3) ◽  
pp. 619-633 ◽  
Author(s):  
J. Fevery ◽  
P. Leroy ◽  
K. P. M. Heirwegh
Keyword(s):  
Enzyme Activities ◽  
Metal Ion ◽  
Glucuronic Acid ◽  
Uridine Diphosphate ◽  
No Formation ◽  
Cell Extracts ◽  
Straight Line ◽  
Standard Assay ◽  
Diphosphate Glucose ◽  
Liver Homogenates

1. Digitonin-treated and untreated homogenates, cell extracts and washed microsomal preparations from liver of Wistar R rats are capable of transferring sugar from UDP-glucose or UDP-xylose to bilirubin. No formation of bilirubin glycosides occurred with UDP-galactose or d-glucose, d-xylose or d-glucuronic acid as the sources of sugar. 2. Procedures to assay digitonin-activated and unactivated bilirubin UDP-glucosyltransferase and bilirubin UDP-xylosyltransferase were developed. 3. In digitonin-activated microsomal preparations the transferring enzymes had the following properties. Both enzyme activities were increased 2.5-fold by pretreatment with digitonin. They were optimum at pH6.6–7.2. Michaelis–Menten kinetics were followed with respect to UDP-glucose. In contrast, double-reciprocal plots of enzyme activity against the concentration of UDP-xylose showed two intersecting straight-line sections corresponding to concentration ranges where either bilirubin monoxyloside was formed (at low UDP-xylose concentrations) or where mixtures of both the mono- and di-xyloside were synthesized (at high UDP-xylose concentrations). Both enzyme activities were stimulated by Mg2+; Ca2+ was slightly less, and Mn2+ slightly more, stimulatory than Mg2+. Of the activities found in standard assay systems containing Mg2+, 58–78% (substrate UDP-glucose) and 0–38% (substrate UDP-xylose) were independent of added bivalent metal ion. Double-reciprocal plots of the Mg2+-dependent activities against the concentration of added Mg2+ were linear. 4. In comparative experiments the relative activities of liver homogenates obtained with UDP-glucuronic acid, UDP-glucose and UDP-xylose were 1:1.5:2.7 for untreated preparations and 1:0.29:0.44 after activation with digitonin. 5. Bilirubin UDP-glucuronyltransferase was protected against denaturation by human serum albumin, whereas bilirubin UDP-xylosyltransferase was not. 6. Digitonin-treated and untreated liver homogenates from Gunn rats were inactive in transferring sugar to bilirubin from UDP-glucuronic acid (in agreement with the work of others), UDP-glucose or UDP-xylose.

scholarly journals Everything You Always Wanted to Know about β3-AR * (* But Were Afraid to Ask)

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 357 ◽  
Author(s):  
Giorgia Schena ◽  
Michael J. Caplan
Keyword(s):  
Adrenergic Receptor ◽  
Species Differences ◽  
Current Clinical Practice ◽  
Substantial Body ◽  
Cellular Models ◽  
Wide Range ◽  
The Subject ◽  
And Function ◽  
Novel Therapeutic ◽  
Do So

The beta-3 adrenergic receptor (β3-AR) is by far the least studied isotype of the beta-adrenergic sub-family. Despite its study being long hampered by the lack of suitable animal and cellular models and inter-species differences, a substantial body of literature on the subject has built up in the last three decades and the physiology of β3-AR is unraveling quickly. As will become evident in this work, β3-AR is emerging as an appealing target for novel pharmacological approaches in several clinical areas involving metabolic, cardiovascular, urinary, and ocular disease. In this review, we will discuss the most recent advances regarding β3-AR signaling and function and summarize how these findings translate, or may do so, into current clinical practice highlighting β3-AR’s great potential as a novel therapeutic target in a wide range of human conditions.

Some species differences in the intrinsic factor stimulation of B12 uptake by small intestine in vitro

1959 ◽  
Vol 197 (4) ◽  
pp. 926-928 ◽  
Author(s):  
T. Hastings Wilson ◽  
Elliott W. Strauss
Keyword(s):  
Small Intestine ◽  
Guinea Pig ◽  
Species Differences ◽  
Intrinsic Factor ◽  
Vitamin B ◽  
Guinea Pig Ileum ◽  
Rat Intestine ◽  
Intrinsic Factors ◽  
Stimulation Of

Sacs of everted small intestine from a variety of animals were incubated in bicarbonate-saline containing vitamin B12 with and without intrinsic factor (IF). B12 uptake by rat intestine was stimulated only by its own intrinsic factor. Guinea pig ileum responded to all intrinsic factors tested (guinea pig, rat, hog, hamster, human being and rabbit). The intestines of hamster and rabbit were intermediate in specificity, responding to some, but not all, of the IF preparations. Species differences occur in both the intestine and intrinsic factor preparations. The guinea pig ileum was suggested as a possible assay for both hog and human IF.

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