Fate of tritium-labeled carnitine administered to dogs and rats

1962 ◽  
Vol 202 (1) ◽  
pp. 122-128 ◽  
Author(s):  
Kenneth T. N. Yue ◽  
Irving B. Fritz

dl-Carnitine hydrochloride, tritiated nonspecifically, was purified and shown to have the same chemical and biological properties as the original compound (ß-hydroxy, γ-trimethylammonium butyrate). About one-third of administered material was excreted in urine during a 7-hr period following the intravenous injection of carnitine HCl (2 mg/kg) to dogs. Tritium not excreted appeared primarily in the trichloroacetic acid (TCA)-soluble fraction of various tissues, with approximately half that administered being found in skeletal muscle. The concentrations of tritium in TCA-soluble fractions of all organs examined except brain were 4–30 times higher than plasma concentrations. No evidence of carnitine degradation was found. The tritiated material in TCA-soluble extracts moved as single peaks in three different chromatographic systems, having the same RF values as those of known samples of carnitine. Tritium in chloroform-soluble fractions accounted for less than 1% of that administered. Of the organs examined, liver had the highest relative amount of incorporation of tritium into lipids, with all activity being found in unidentified phospholipids, chiefly in the lecithin fraction. The possible physiological significance of carnitine in muscle is briefly discussed.

1970 ◽  
Vol 119 (4) ◽  
pp. 651-657 ◽  
Author(s):  
Ramadasan Kuttan ◽  
A. N. Radhakrishnan

1. trans-4-Hydroxy-l-proline was found to occur in the bound state in the leaves of sandal (Santalum album L.), in which large amounts of free cis-4-hydroxy-l-proline are also present. 2. Bound trans-4-hydroxy-l-proline was present, associated mainly with a `wall' fraction and a `soluble' fraction roughly in equal proportions. 3. Bound proline is present only in small amounts in the `soluble' fraction but is mostly associated with the `wall' fraction and the other sedimented fractions. 4. In the free amino acid fraction more than 98% of the hydroxyproline had the cis-configuration, whereas in the `wall' and `soluble' fractions more than 90% of the bound hydroxyproline was in the trans-configuration. 5. Various extraction procedures indicated heterogeneity of the hydroxyproline-containing components. Hot 5% (w/v) trichloroacetic acid extracts about 25% of hydroxyproline and m-NaOH extracts an additional 25%. 6. Incorporation of [14C]proline into the bound hydroxyproline was demonstrated. The hydroxyproline component of the `soluble' fraction does not appear to be the precursor of that of the `wall' fraction.


PEDIATRICS ◽  
1959 ◽  
Vol 24 (1) ◽  
pp. 74-91
Author(s):  
Zacharias Dische ◽  
Paul di Sant'Agnese ◽  
Charles Pallavicini ◽  
Joshua Youlos

The mucus of the duodenal fluid of children contains a mixture of carbohydrateprotein complexes with the character of mucoids and glycoproteins. In duodenal fluids from patients with cystic fibrosis of the pancreas about one-third in controls about 90%, of the mucoid material is soluble in trichloroacetic acid (TCA). In duodenal fluids from patients with cystic fibrosis about one-third of the mucoid becomes denatured and insoluble in water when precipitated with an ethanolbenzene mixture. The TCA-soluble mucoid from patients with cystic fibrosis and controls was separated by fractionated ethanol precipitation into four fractions: three precipitating at 50% (A); 67% (B); and 90% (C), respectively; and one soluble in 90% ethanol. All four fractions contain as carbohydrate moiety a fucomucopolysaccharide. Fractions C and D contain about equivalent amounts of galactose and mannose and in patients with cystic fibrosis only one hexosamine (glucosamine) in demonstrable amounts. Fractions A and B contain glucosamine as well as galactosamine in comparable amounts, but the hexose present is galactose to an extent of more than 80%. The polysaccharides of all four mucoid fractions differ in their content of sialic acid. The least-soluble fraction A contains less of it than the more soluble fractions. The content of sialic acid in the mucopolysaccharide of the water-insoluble mucoid, and of the TCA-insoluble water-soluble fraction from pooled duodenal fluids of patients with cystic fibrosis, approaches that of fraction A and is lower than that of other fractions. The molar ratio of fucose to hexosamine in fraction A, and in the water-insoluble mucoid from patients with cystic fibrosis, is higher than in all fractions from controls.


1961 ◽  
Vol 06 (01) ◽  
pp. 157-159 ◽  
Author(s):  
Saul B. Gilson

ConclusionExperimental glomerulitis in rabbits following intravenous injection of gamma globulin was inhibited by heparinization. The physiological and patho-physiological significance of this observation is considered.


1969 ◽  
Vol 61 (3) ◽  
pp. 432-440 ◽  
Author(s):  
Ingvar Sjöholm ◽  
Gunnar Rydén

ABSTRACT The distribution of oxytocin in the kidneys, liver, uterus and skeletal muscle of the rat was followed during 10 min after intravenous injection of tritium labelled oxytocin. Oxytocin was found to be taken up and degraded mainly in the kidneys and the liver. After 150 seconds no intact oxytocin could be detected in these organs. The time course of the distribution of the radioactivity in the liver and the skeletal muscle showed no noteworthy characteristics, whereas a different course was found in the kidneys and in the uterus. In the kidneys, the radioactivity increased continuously from 60 to 200 seconds after the injection, indicating an accumulation of oxytocin or its metabolites in the kidneys. In the uterus a high initial uptake was observed, followed by a decrease of the radioactivity from 60 to 100 seconds after the injection. This distribution pattern was specific to oxytocin, since the uptake of tritiated tyrosine and tritiated water was almost constant during the same time period. These findings may indicate a preferential distribution of oxytocin to the uterus.


1991 ◽  
Vol 65 (1) ◽  
pp. 47-60 ◽  
Author(s):  
D. Dardevet ◽  
M. Manin ◽  
M. Balage ◽  
C. Sornet ◽  
J. Grizard

The influence of protein content of the diet on the plasma concentrations and binding to skeletal muscle and liver of insulin and insulin-like growth factor-1 (IGF-1), was studied in growing rats. Animals with a starting body-weight of 80 g received for an 11 d period isoenergetic diets containing (g/kg dry matter) 155 protein as controls (MP), or 55 (LP) or 300 (HP) protein. Food was offered as six equal meals/d. Daily food intakes provided adequate amounts of energy. Total plasma IGF-1 increased linearly as a function of dietary protein intake. Plasma insulin was lower in the LP than in the MP and HP groups. Hormone binding was studied in wheat-germ agglutinin (WGA) partially purified skeletal muscle receptor preparations. Each 125I-labelled hormone binding was competed for by increasing amounts of homologous and heterologous unlabelled hormone; this displacement needed lower concentrations of homologous than heterologous hormone. When compared with MP-diet feeding, the LP diet resulted in an increased ligand concentration for half-maximal binding. In addition the specific 125I-labelled insulin and 125I-labelled IGF-1 binding increased at all hormone concentrations and, as revealed by Scatchard analysis, the hormone binding capacity also rose (only significant for low-affinity insulin receptors and high-affinity IGF-1 receptors). The HP diet had little effect on hormone binding, except to increase insulin binding at very low insulin concentrations. Hormone binding was further studied in WGA partially purified liver receptor preparations. Those preparations did not exhibit any detectable specific 125I-labelled IGF-1 binding. The specific 125I-labelled insulin binding was not altered by dietary protein level. It is concluded that the increase in skeletal muscle insulin and IGF-1 binding along with a decrease in insulin and IGF-1 in the blood from rats fed on the LP diet, is consistent with the concept of an inverse relationship between plasma hormone and hormone binding. The physiological significance with respect to metabolic adaptation of muscle remains to be established


1993 ◽  
Vol 264 (1) ◽  
pp. E1-E10 ◽  
Author(s):  
L. Rossetti ◽  
S. Farrace ◽  
S. B. Choi ◽  
A. Giaccari ◽  
L. Sloan ◽  
...  

Calcitonin gene-related peptide (CGRP) is a neuropeptide that is released at the neuromuscular junction in response to nerve excitation. To examine the relationship between plasma CGRP concentration and intracellular glucose metabolism in conscious rats, we performed insulin (22 pmol.kg-1.min-1) clamp studies combined with the infusion of 0, 20, 50, 100, 200, and 500 pmol.kg-1.min-1 CGRP (plasma concentrations ranging from 2 x 10(-11) to 5 x 10(-9) M). CGRP antagonized insulin's suppression of hepatic glucose production at plasma concentrations (approximately 10(-10) M) that are only two- to fivefold its basal portal concentration. Insulin-mediated glucose disposal was decreased by 20-32% when CGRP was infused at 50 pmol.kg-1.min-1 (plasma concentration 3 x 10(-10) M) or more. The impairment in insulin-stimulated glycogen synthesis in skeletal muscle accounted for all of the CGRP-induced decrease in glucose disposal, while whole body glycolysis was increased despite the reduction in total glucose uptake. The muscle glucose 6-phosphate concentration progressively increased during the CGRP infusions. CGRP inhibited insulin-stimulated glycogen synthase in skeletal muscle with a 50% effective dose of 1.9 +/- 0.36 x 10(-10) M. This effect on glycogen synthase was due to a reduction in enzyme affinity for UDP-glucose, with no changes in the maximal velocity. In vitro CGRP stimulated both hepatic and skeletal muscle adenylate cyclase in a dose-dependent manner. These data suggest that 1) CGRP is a potent antagonist of insulin at the level of muscle glycogen synthesis and hepatic glucose production; 2) inhibition of glycogen synthase is its major biochemical action in skeletal muscle; and 3) these effects are present at concentrations of the peptide that may be in the physiological range for portal vein and skeletal muscle. These data underscore the potential role of CGRP in the physiological modulation of intracellular glucose metabolism.


1983 ◽  
Vol 36 (3) ◽  
pp. 295 ◽  
Author(s):  
NR Adams ◽  
GB Martin

The effects of oestradiol on plasma luteinizing hormone (LH) concentrations were examined in 15 ovariectomized control ewes and 15 similar ewes with permanent infertility after prolonged grazing on oestrogenic clover pasture ('clover disease'). Before treatment, the plasma concentrations of LH were similar in the control and affected ewes. After intravenous injection with 40 pg oestradiol-I 7 p during the anoestrous season, the decline in LH concentration was greater in the clover-affected ewes and the subsequent elevation above original baseline levels was smaller. After intramuscular injection with 15 or 30 pg oestradiol benzoate during the normal breeding season, fewer clover-affected ewes showed a surge of LH, and the response was both reduced and retarded. This difference between the two groups has not been observed in studies on intact ewes, and it is suggested that in intact ewes the difference is masked by a greater tonic LH activity in affected ewes. The results of the present study are consistent with the hypothesis that prolonged exposure to oestrogenic pasture has a differentiating, or 'androgenizing' effect on the adult ewe.


Author(s):  
Geoffrey Warnier ◽  
Estelle De Groote ◽  
Florian A. Britto ◽  
Ophélie Delcorte ◽  
Joshua P. Nederveen ◽  
...  

Purpose: To investigate exosome-like vesicle (ELV) plasma concentrations and markers of multivesicular body (MVB) biogenesis in skeletal muscle in response to acute exercise. Methods: Seventeen healthy (BMI: 23.5±0.5kg·m-2) and fifteen prediabetic (BMI: 27.3±1.2kg·m-2) men were randomly assigned to two groups performing an acute cycling bout in normoxia or hypoxia (FiO2 14.0%). Venous blood samples were taken before (T0), during (T30) and after (T60) exercise and biopsies from m. vastus lateralis were collected before and after exercise. Plasma ELVs were isolated by size exclusion chromatography, counted by nanoparticle tracking analysis (NTA), and characterized according to international standards, followed by expression analyses of canonical ELV markers in skeletal muscle. Results: In the healthy normoxic group, the total number of particles in the plasma increased during exercise from T0 to T30 (+313%) followed by a decrease from T30 to T60 (-53%). In the same group, an increase in TSG101, CD81 and HSP60 protein expression was measured after exercise in plasma ELVs; however, in the prediabetic group, the total number of particles in the plasma was not affected by exercise. The mRNA content of TSG101, ALIX and CD9 were upregulated in skeletal muscle after exercise in normoxia; whereas, CD9 and CD81 were downregulated in hypoxia. Conclusions: ELV plasma abundance increased in response to acute aerobic exercise in healthy subjects in normoxia, but not in prediabetic subjects, nor in hypoxia. Skeletal muscle analyses suggested that this tissue did not likely play a major role of the exercise-induced increase in circulating ELVs.


1989 ◽  
Vol 257 (6) ◽  
pp. H1812-H1818 ◽  
Author(s):  
G. K. Savard ◽  
E. A. Richter ◽  
S. Strange ◽  
B. Kiens ◽  
N. J. Christensen ◽  
...  

The purpose of this study was to determine the effect of increasing muscle mass involvement in dynamic exercise on both sympathetic nervous activation and local hemodynamic variables of individual active and inactive skeletal muscle groups. Six male subjects performed 15-min bouts of one-legged knee extension either alone or in combination with the knee extensors of the other leg and/or with the arms. The range of work intensities varied between 24 and 71% (mean) of subjects' maximal aerobic capacity (% VO2max). Leg blood flow, measured in the femoral vein by thermodilution, was determined in both legs. Arterial and venous plasma concentrations of norepinephrine (NE) and epinephrine were analyzed, and the calculated NE spillover was used as an index of sympathetic nervous activity to the limb. NE spillover increased gradually both in the resting, and to a larger extent in the exercising legs, with a steeper rise occurring approximately 70% VO2max. These increases were not associated with any significant changes in leg blood flow or leg vascular conductance at the exercise intensities examined. These results suggest that, as the total active muscle mass increases, the rise in sympathetic nervous activity to skeletal muscle, either resting or working at a constant load, is not associated with any significant neurogenic vasoconstriction and reduction in flow or conductance through the muscle vascular bed, during whole body exercise demanding up to 71% VO2max.


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