Turnover In Rats Research Articles

The acute effects of sulpiride on the central dopamine turnover in rats: a quantitative histochemical study.

Sulpiride accelerated the dopamine turnover preferentially in the mesolimbic as compared to the nigrostriatal dopamine system. However, the tuberoinfundibular dopamine turnover was not affected by sulpiride or haloperidol.

Regulation of hepatic glutathione turnover in rats in vivo and evidence for kinetic homogeneity of the hepatic glutathione pool.

The intracellular distribution of glutathione into kinetically distinct pools and the determinants of glutathione turnover were examined in vivo. Glutathione turnover was measured in individual, restrained rats with a biliary fistula by administration of acetaminophen to trap the previously labeled hepatic glutathione as an excretable acetaminophen adduct. Fasting for 48 h resulted in a decrease of hepatic glutathione from 4.7+/-0.9 to 3.6+/-0.8 mumol/g liver and a marked increase in the fractional rate of glutathione turnover from 0.19+/-0.04 to 0.43+/-0.07/h. Within 6 h following refeeding, the rate of glutathione turnover and the hepatic glutathione concentration returned to normal. The simultaneously determined specific activities of free intrahepatic glutathione and the acetaminophen-glutathione adduct in bile were identical, indicating that the hepatic glutathione pool is kinetically homogeneous. The synthesis of glutathione could, therefore, be estimated from the rate constant and the intrahepatic glutathione concentration. During fasting hepatic synthesis of glutathione increased from 0.86+/-0.17 to 1.50+/-0.23 mumol/g per h. In fed animals the administration of dibutyryl cyclic adenosine monophosphate and theophylline stimulated the rate of hepatic glutathione turnover similar to fasting. In contrast, glucose given intraduodenally to fasted animals decreased the rate of glutathione turnover. These data are consistent with the view that the increased glutathione turnover that occurs during fasting results from two mechanisms. Because of a decrease in the intrahepatic free glutathione/mixed disulfide ratio, which is apparently mediated by cyclic adenosine monophosphate, the free glutathione pool contracts and turns over more rapidly in order to maintain glutathione synthesis. In addition, glutathione consumption via the gamma-glutamyl cycle apparently is increased, which may be related to the increased uptake of amino acids for gluconeogenesis during fasting.

Reduction of hippocampal acetylcholine turnover in rats treated with (−)-Δ 8-tetrahydrocannabinol and its 1′,2′-dimethyl-heptyl homolog

The effects of (-)-delta 8-tetrahydrocannabinol (THC), (+)-delta 8-THC, and the dimethyl-heptyl (DMH) homolog of (-)-delta 8-THC (delta 8-THC-DMH) have been compared with the action of (-)-delta 9-THC on the turnover rate of acetylcholine in various brain areas. The data demonstrate that (-)-delta 8-THC-DMH, (-)-delta 9-THC and (-)- delta 8-THC all specifically reduce ther turnover rate of acetylcholine in the hippocampus in a dose-dependent manner ((-)-delta 8-THC-DMH > (-)-delta 9-THC > (-)-delta 8-THC) without altering the acetylcholine or choline content (except for high doses of (-)-delta 8-THC-DMH). The (+)-isomer of delta 8-THC fails to change any cholinergic parameter. The selectivity of action suggests that the tetrahydrocannabinoids may activate specific transmitter receptors which indirectly modulate the activity of the cholinergic neurons in the septal-hippocampal pathway.

Nutritional Interrelationships Between Calcium, Phosphorus and Lactose in Rats

From the age of 3 months, six groups of rats consisting of six animals each were fed one of three types of diet with either 15% lactose or dextrose. The diets used were a control diet containing 0.6% calcium and 0.45% phosphorus and two high-phosphorus (1.3%) diets with either a normal (0.6%) or a low (0.2%) calcium content. Whereas calcium retention and femur mass appeared to be unaffected, feeding the high-phosphorus diets resulted in significant (P less than or equal to 0.05 or P less than or equal to 0.01) biochemical changes including: decreased plasma phosphorus almost throughout the whole of the study; increased plasma alkaline phosphatase, and urinary total hydroxyproline after 17 and 42 weeks; nephrocalcinosis; depressed urinary calcium, and reduced femur density. With the excretion of nephrocalcinosis and depressed urinary calcium, these changes were more marked if the calcium content of the diet was low than when it was normal, and this difference was associated with a significant (P less than 0.01) inhibiting effect of dietary calcium on the intestinal absorption and urinary excretion of phosphorus. Although lactose, as compared with dextrose, significantly (P less than 0.01) improved the intestinal absorption and retention of calcium during body weight gain, which was reflected by an increased femur mass after 42 weeks, this sugar did not reduce the detrimental effects on bone and soft tissue resulting from feeding the high-phosphorus diets. The results of the study in line with the induction of nutritional secondary hyperparathyroidism and increased bone turnover in rats fed high-phosphorus diets and indicate that lactose-stimulated calcium absorption will not prevent or diminish the biochemical changes associated with this disease; the results also stress the significance of the calcium content of the diet as a factor that may protect the body against excessive dietary phosphorus.

Metabolism of hepatic haem and 'green pigments' in rats given 2-allyl-2-isopropylacetamide and ferric citrate. A new model for hepatic haem turnover.

We have studied effects of single doses of 2-allyl-2-isopropylacetamide and ferric citrate on hepatic haem turnover in rats. Haem was pre-labelled by intraperitoneal administration of 5-amino-[4-(14)C]laevulinate 4h before other treatments. Computer-assisted analysis of the haem decay curve showed that at least two exponential components were involved implying two haem pools. In control rats the size of the rapidly-turning-over pool was 38% of the total. Treatment with 2-allyl-2-isopropylacetamide alone resulted in a 2.3-fold increase in the fractional size of this pool. Treatment with ferric citrate alone increased the size of this pool 1.8-fold; treatment with both agents together had no measurable effect beyond that produced by 2-allyl-2-isopropylacetamide. The apparent rate constant for disappearance of labelled haem from the first pool was not affected by treatment with 2-allyl-2-isopropylacetamide or ferric citrate, indicating that these treatments affect hepatic haem turnover primarily by altering the distribution of haem synthesized in the liver. The increased haem degradation after treatment with 2-allyl-2-isopropylacetamide alone was associated with the accumulation of ;green pigments' in the liver. These pigments were detectable 1.5h after drug treatment; their total amount increased steadily for 28h and then declined. Despite this increase in amount, radioactivity of the ;green pigment' fraction fell rapidly in a biphasic fashion. Some of the radioactivity that initially was found in the ;green pigment' fraction was later found in an aqueous fraction, not extractable by acidic ethyl acetate. Rats given ferric citrate together with 2-allyl-2-isopropylacetamide accumulated less ;green pigments'.

Essential fatty acid deficiency and plasma triglyceride turnover in rats.

Hepatic triglyceride secretion in essential fatty acid-deficient rats was examined by three separate techniques in an effort to resolve conflicting evidence on the question of whether essential fatty acid deficiency altered hepatic triglyceride secretion in vivo. First, plasma triglyceride turnover was measured by intravenous injection of [2-3H]glycerol trioleate. Equations of the kinetics were formulated based on a single, open pool model. Turnover rates and pool sizes of plasma triglyceride were calculated from these equations. Second, [2-3H]glycerol was injected, and apparent rate constants for plasma triglyceride secretion and clearance were calculated by kinetic analysis. Third, Triton WR-1339 was used to inhibit lipoprotein clearance from blood plasma, and rates of plasma triglyceride accumulation were measured. The results of these studies showed that the rate of hepatic triglyceride secretion was 2-3 times greater in essential fatty acid-deficient rats than in nondeficient controls. The increase in triglyceride secretion, as well as the higher level of liver triglyceride typical of essential fatty acid-deficient rats, could be caused by increased lipogenesis and increased mobilization of fatty acids from adipose tissues.

Effect of fasting on glucose, lactate and alanine turnover in rats and guinea-pigs

-1. Blood glucose and lactate levels were comparable in fed rats and guinea-pigs but blood alanine was three times higher in rats than in guinea-pigs. 2. After a 48 hr fasting period blood concentration and turnover rates of glucose, lactate and alanine decreased in rats. 3. After a 48 hr fasting period blood concentration and turnover rates of glucose and lactate did not vary in guinea-pigs whereas blood alanine and alanine turnover increased. 4. Increased availability of glucose precursors and a better efficiency of gluconeogenic processes in fasted guinea-pigs compared to fasted rats may explain in part the different variation of blood glucose and glucose turnover rate during starvation in the two species.

Effect of apomorphine on morphine-induced decrease in locomotor activity and increase in dopamine turnover in rats.

Effect of apomorphine on morphine-induced decrease in locomotor activity and increase in dopamine turnover in rats.

The effect of surgical trauma on muscle protein turnover in rats. A serious methodological misunderstanding.

The reported rates of protein degradation in a recent paper on the effect of surgical trauma on muscle protein turnover [Hoover-Plow & Clifford (1978) Biochem. J. 176, 137--142] have no real meaning because of a serious methodological misunderstanding by the authors. In addition, there are problems involved in the determination of synthesis rates, so that the reported effects of trauma on muscle protein turnover can be discounted.

Effects of (8β)-8-[(Methylthio)methyl]-6-propylergoline on dopaminergic function and brain dopamine turnover in rats

(8β)-8-[(Methylthio)methyl]-6-propylergoline induced contralateral turning in rats with nigrostriatal lesions, lowered serum prolactin in reserpinized rats, and caused stereotyped hyperactivity. In addition to these functional effects typical of dopaminergic agonists, (8β)-8-[(methylthio)methyl]-6-propylergoline decreased dopamine turnover in rat brain. Decreased turnover was indicated by a diminished depletion of dopamine content after inhibition of its synthesis by α-methyltyrosine and by a decreased steady state concentration of the dopamine metabolite, 3, 4-dihydroxyphenylacetic acid (DOPAC). DOPAC concentration in whole brain was decreased after doses of (8β)-8-[(methylthio)methyl]-6-propylergoline as low as 0.003 mg/kg, and the lowering of DOPAC persisted for up to 16 hrs. after a 0.3 mg/kg dose. (8β)-8-[(Methylthio)-methyl]-6-propylergoline had less effect than a structurally-related compound, lergotrile, on 3-methoxy-4-hydroxy-phenyl-ethyleneglycol sulfate levels in whole brain and did not affect 5-hydroxy-indoleacetic acid levels over a dose range from .01–10 mg/kg. The behavioral and neuroendocrine effects of this new ergoline compound and its reduction of dopamine turnover in rat brain indicate that it is a potent dopamine receptor agonist in vivo .

Circadian changes in norepinephrine turnover in rats following administration of estrogen

1. Circadian changes in norepinephrine (NE) turnover were found in 4-month-old rats following administration of estrogen. 2. In the hypothalamus NE turnover occurred in the late-dark period only in mestranol-treated rats. 3. At the late-dark and early-light phases NE turnover was found to occur in the cerebellum of control rats, but was not found in mestranol-treated rats at these times nor in the mid-light period. 4. Following estrogen treatment adrenal NE turnover was discovered at early- and mid-light phases. 5. Cardiac NE turnover was not found to occur in mestranol-treated rats at any of the three times sampled.

The effect of surgical trauma on muscle protein turnover in rats.

The rate of synthesis and catabolism of sarcoplasmic- and myofibrillar-muscle protein was measured in operated, sham-operated and food-restricted rats by using Na2 14CO3. The food-restricted group underwent sham operations and were limited to the food intake of the operated animals. Protein synthesis and catabolism were increased in the sarcoplasmic-muscle fraction in operated rats compared with that in sham-operated or food-restricted rats. The rate of synthesis of the myofibrillar protein decreased in operated animals, but the rate of catabolism was not altered in the myofibrillar-muscle fraction of the operated animals compared with that in food-restricted and sham-operated animals. In the operated animals, there was a net loss of protein from the muscle. Thus the rats that underwent surgery lost muscle protein, primarily as a result of a decrease in synthesis of myofibrillar protein. The changes in protein turnover in operated animals were not due to decreases in food intake, since protein turnover in sham-operated animals that were restricted to the food intake of the operated rats was not different from that in sham-operated rats fed ad libitum.

Effect of Pectin, Gum Arabic and Agar on Cholesterol Absorption, Synthesis, and Turnover in Rats

A series of five experiments was conducted to determine the effect of pectin, gum arabic and agar (5%) on cholesterol absorption, biosynthesis and turnover in rats. In the study of cholesterol absorption, a tracer dose of labeled cholesterol was included in the last meal. The rats were killed 12 hours later. The proportion of the labeled cholesterol recovered in the whole body was used as an estimation of the efficiency of absorption of dietary cholesterol. Cholesterol biosynthesis was estimated by determining the activity of labeled digitonin-precipitable sterols biosynthesized from labeled glucose which was included in a test meal. In turnover studies, rats were injected intravenously with labeled cholesterol using serum as a vehicle, and the activity of labeled cholesterol in tissues was determined after various time intervals. All three complex carbohydrates decreased cholesterol absorption and pectin had the greatest effect. Pectin and gum arabic increased cholesterol biosynthesis in rats fed a cholesterol-containing diet, but had no effect in a cholesterol-free diet. Pectin slightly increased the turnover of cholesterol, but gum arabic and agar had no effect. This work supports the hypothesis that pectin lowers cholesterol levels by interfering with cholesterol absorption and by increasing cholesterol turnover. The study also suggests that complex carbohydrates differ in their effects on cholesterol metabolism. The reason for these differences remains to be determined.

42) - Effects of intracerebral injection of gabaculine on behaviour and dopamine turnover in rats

42) - Effects of intracerebral injection of gabaculine on behaviour and dopamine turnover in rats

Effects of pyrroxan and chlordiazepoxide on biogenic amine metabolism in the rat brain

Pyrroxan (20 mg/kg, i.p.), a new potential antianxiety agent, increased brain norepinephrine (NE) turnover in rats, reflecting a possible central alpha-adrenergic receptor blocking activity. In contrast, chlordiazepoxide (20 mg/kg, i.p.), a widely used antianxiety agent, did not alter the NE turnover. Pyrroxan did not affect overall DA turnover although it did appear to accelerate DA turnover initially. The initial potentiation of DA turnover may indicate a short-lasting blocking action on DA receptors. In comparison, chlordiazepoxide (20 mg/kg, i.p.) decreased the turnover rate of DA. Effects of both drugs on 5-HT indicate a decrease in turnover with no significant monoamine oxidase activity or blockade of the 5-HT reuptake mechanism. Both drugs antagonized the decline in intraventicularly-injected 14C-5-HT. Neither drug caused consistent changes in endogenous 5-HT, 5-hydroxyindoleacetic acid, or tryptophan levels. Neither drug potentiated the behavioral effects of L-Dopa nor increased the 5-HTP behavoiral syndrome in the mouse. Pyrroxan may be expected to exhibit a spectrum of activity between that of minor and major tranquilizers, characterized by antianxiety action together with sedative or tranquilizing activity.

Reversible and irreversible phases of serotonin depletion by 4-chloroamphetamine

Pretreatment of rats with an agent that inhibits uptake into serotoninergic neurons [Lilly 110140:3-(p-trifluoromethylphenoxy)-N-methyl-3- phenylpropylamine hydrochloride] prevented the depletion of brain serotonin by 4-chloroamphetamine, presumably by preventing the entry of 4-chloroamphetamine into the serotonin neuron. When the uptake inhibitor was given after 4-chloroamphetamine, the lowering of both serotonin and tryptophan hydroxylase levels in brain was reversed. Serotonin levels returned to normal after 110140 administration to 4-chloroamphetamine-treated rats at a rate similar to the calculated rate of serotonin turnover in rats treated with 110140 alone. Progressively less reversibility of the 4-chloroamphetamine effect occured when 110140 was injected at 8, 16 and 24 hr after 4-chloroamphetamine, and no reversibility was observed when 110140 was injected at 32 or 48 hr after 4-chloroamphetamine. These findings indicate that the depletion of brain serotonin by 4-chloroamphetamine is initially reversible but that there is a gradual transition into an irreversible effect between 24 and 48 hr after 4-chloroamphetamine injection. Apparently the prolonged presence of 4-chloroamphetamine inside the serotonin neuron produced by continual reuptake of 4-chloroamphetamine is required to the semi-permanent depletion of brain serotonin stores.

Enhancement of cholesterol turnover in rats by a catatoxic steroid (PCN) and a bile acid sequestrant (colestipol-HCl)

Catatoxic steroids induce hepatic microsomal enzymes. To determine if cholesterol catabolism to bile acids by microsomal enzymes is stimulated by a catatoxic steroid, effects of pregnenolone-16α-carbonitrile (PCN) alone or with colestipol-HCl on cholesterol 7α-hydroxylase, cholesterol synthesis and cholesterol turnover were studied. Male rats fed diets containing colestipol (1%), PCN (0.085%), colestipol plus PCN, or basic diet were injected with [1,2,- 3H]-cholesterol complexed with serum lipoproteins. Serum cholesterol specific radioactivity was measured for 49 days. Hepatic cholesterol and bile acid synthesis were estimated by [1- 14C]-acetate incorporation and cholesterol 7α-hydroxylase activity. Turnover curves were analyzed using a three-pool model. PCN significantly increased all rate constants and cholesterol production rate (10.75 to 12.87 mg/day), which in this model is a measure of total body cholesterol turnover. Colestipol significantly increased total body cholesterol turnover (10.75 to 19.91 mg/day) and the excretion rate constant (0.44 to 0.88 day −1) and increased acetate incorporation 6-fold and cholesterol 7 α-hydroxylase activity 2-fold. PCN only slightly inhibited the latter. Effects of colestipol plus PCN were not different from those of colestipol alone. No treatment significantly changed cholesterol serum levels overall. Colestipol results are consistent with reported data for bile acid sequestrants. PCN markedly increased cholesterol flux between pools; it does not appear to induce and may, in fact, inhibit bile acid synthesis, perhaps by decreasing availability of necessary cofactors or cholesterol substrate.

Determination of Carnitine Turnover in Choline-deficient and Cold-exposed Rats

Two experimetns were conducted to study the body pool size and turnover rate of carnitine in rats. The turnover of carnitine was determined by injection of a tracer dose of L-[methyl-14C] carnitine. In experiment 1, carnitine body pool size and turnover in rats fed a choline-deficient basal diet were compared with values obtained from rats fed the basal diet supplemented with choline. These rats were maintained at 22degrees. In experiment 2, carnitine body pool size and turnover were determined in cold-exposed (2degrees) rats fed the choline-deficient basal diet. Carnitine body pool sizes of rats maintained 22degrees and fed the choline-deficient basal diet and the choline-supplemented diet were 35.6 and 41.8 mumoles/100 g body weight, respectively. Carnitine body pool size of rats maintained at 2degrees and fed a choline-deficient basal diet were 6.6 and 56.1 days, for rats fed a choline-supplemented diet, 6.7 and 40.2 days, and for rats maintained at 2degrees and fed a choline-deficient diet, 2.9 and 36.4 days, respectively. Carnitine turnover times obtained with DL-[14C]carnitine in our previous study longer than turnover times obtained with DL-[14C]carnitine in our previous study (j. nutr. 104, 782-792). These observations suggest that D-carnitine is not metabolized the same way as L-carnitine, and that D-carnitine is not cleared from the body within 2 days after injection. The results also suggest that carnitine metabolism can be influenced by the amount of choline in the diet and by cold exposure.

Significance of Dietary Carnitine for Growth and Carnitine Turnover in Rats

Significance of Dietary Carnitine for Growth and Carnitine Turnover in Rats

Influence of Linoleate on Cholesterol Turnover in Rats

Influence of Linoleate on Cholesterol Turnover in Rats