Effect of antinociceptive doses of oxotremorine on mouse brain acetylcholine turnover rate

The effect of antinociceptive doses of oxotremorine on the steady-state level and turnover rate of acetylcholine (ACh) was investigated in male Swiss-Webster mice. Oxotremorine produced dose-related increases in ACh levels which attained statistical significance (p ≥ 95; Dunnett's T) with the ED₈₄ antinociceptive dose in two sacrifice methods. The increased steady-state level of ACh was temporally correlated with the peak antinociceptive effect of oxotremorine. ACh turnover rate decreased with increasing doses of oxotremorine. The ACh turnover rate decreased from 11.06 ± 1.62 nmol/g/min to 5.38 ± 0.71 nmol/g/min by decapitation method and 30.20 ± 1.8 nmol/g/min to 19.99 ± 1.6 nmol/g/min by the microwave irradiation method (Ed₈₄ oxotremorine doses). The decrease in turnover rate of ACh produced by antinociceptive doses of oxotremorine is of a lesser magnitude than that produced by tremorogenic doses (1,2).     

Determination of cholesterol turnover rate by a one-and two-pool kinetic analysis.

The cholesterol turnover rate in rabbits with alimentary cholesterol atherosclerosis and in guinea-pigs with chronic vitamin C deficiency was studied by a one- and two-pool kinetic analysis. The one-pool analysis yielded exaggeraged values for the turnover rate, but the turnover rate differences between the control and experimental groups in the one- and the two-pool analysis were very similar. One-pool analysis can be used in initial studies to obtain preliminary data on the effect of nutritional, pharmacological and other factors on cholesterol turnover rate.     

Effect of excess dietary histidine on rate of turnover of65Zn in brain of rat

The effect of the chronic administration of histidine on the brain zinc level was examined in growing, male Wistar rats. Using a purified diet, the minimum zinc requirement for normal growth and normal plasma and tissue zinc levels was found to be around 10 ppm. Given this zinc content; the diet was supplemented with 5% and 8% histidine, respectively, or with 10% glycine (as control). Brain zinc was analyzed by measuring the rate of turnover of⁶⁵Zn from 2–4 weeks after a single injection of the tracer. Feeding the diet supplemented with 5% histidine caused a small decrease in the plasma zinc concentration and a slight increase in the rate of turnover of⁶⁵Zn in the cerebrum and the cerebellum as compared to the control group. The animals fed the diet supplemented with 8% histidine became severely zinc deficient (as evidenced by a 50% reduction in the plasma zinc content), however, the rate of turnover of⁶⁵Zn in all brain regions examined was significantly decreased as compared to the control group. The results indicate that histidine has no specific complexing action on the brain zinc.     

Effects of acute and chronic morphine on regional rat brain acetylcholine turnover rate

A simplified method to study the acetylcholine (ACh) turnover rate (TR_ACh) in brain parts of drug treated rats has been presented. In striatum and occipital cortex of rats receiving a large dose of morphine (140 μ moles/kg i.p.) or implanted chronically with morphine pellets, the TR_ACh is influenced in a different manner. The single injection of morphine reduced the synthesis of ACh in cortex but not in striatum. Morphine pellets decreased striatal TR_ACh but failed to alter the TR_ACh in occipital cortex. Naloxone reversed both changes of TR_ACh elicited by morphine although it was devoid of any effect of the synthesis of ACh in rat brain parts. We suggest that morphine may prevent the ACh release from neurons as proposed by others, however, this effect in striatum of rats receiving a single dose of morphine is masked by the simultaneous action of morphine on the dopaminergic nigrostriatal pathway which regulates the turnover rate of striatal ACh.     

Measurement of acetylcholine turnover rate in discrete areas of rat brain

The turnover rate of ACh was estimated in brain stem, two cortical areas and striatum of rat brain. The turnover rate was highest in the striatum (1.3 μmoles/g/hr); lowest in brain stem (0.092 μmoles/g/hr); and intermediate values were observed in limbic and occipital cortex. The highest ACh concentrations were measured in striatum, those in brain stem were intermediate but in the two cortical areas the ACh concentrations were the lowest. The results of the turnover estimations with the finite difference method yielded values similar to those obtained with the procedure described in this paper. Moreover, once the baseline was established, this method could be reliably used to estimate turnover rate using a single infusion time. The latter simplication would be very useful to compare ACh turnover rate in drug studies.     

Measurement of 5HT turnover rate in discrete nuclei of rat brain

Five non-isotopic methods of measuring serotonin turnover rate in vivo were compared in discrete nuclei of rat brain. The concentration of serotonin or 5-hydroxyindoleacetic acid was measured by high pressure liquid chromatography in the raphe nuclei, caudate nucleus and hippocampus of rats at various times after the injection of pargyline, probenecid, RO 4/4602 or α-propyldopacetamide. The turnover rate is more rapid in the cell bodies than in axon terminals.     

Tryptophan and serotonin turnover rate in the brain of genetically hyperammonemic mice

An investigation was made into the effects of hyperammonemia on the metabolism of brain serotonin (5-HT). The animal model used was the sparse fur (spf) mouse, which possesses an inborn error of the urea cycle, i.e. an abnormal form of ornithine transcarbamylase. Several indoles were measured in brain and plasma using liquid chromatography with electrochemical detection coupled to an u.v. detection (LCEC-u.v.). In the mutant mice, plasma total tryptophan (TRP) was higher when compared with the controls, while plasma free-TRP portion was unchanged. In these animals, brain TRP was increased whilst the 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels were significantly higher in the hypothalamus and midbrain. Experiments with NSD-1015 (100 mg/kg i.p.) indicated that the 5-hydroxytryptophan (5-HTP) synthesis rate was increased in the hyperammonemic mice. Pargyline experiments (100 mg/kg i.p.) confirmed the enhanced brain 5-HT turnover rate in the spf mice. In addition, these experiments led to the conclusion that hyperammonemia does not affect the various rate constants. After administration of NSD-1015, TRP level slightly increased in the spf mouse brains, while it was stationary in those of the controls. This result could indicate an increased activity of hepatic TRP-pyrrolase in the hyperammonemic mice. Valine (VAL) administration (200 mg/kg i.p.) reduced brain TRP content in the two kinds of mice, but its effect was of shorter duration in the spf when compared with the control. Comparison of brain tryptamine level indicated a slight but not significant increase in the mutant mice. The data reported here indicate that hyperammonemia may affect peripheral TRP metabolism with consequences upon brain 5-HT synthesis, which could promote certain neurologic disorders.     

Effect of disulfiram on turnover of 5-hydroxytryptamine in rat brain.

Effect of disulfiram on 5-hydroxytryptamine (5-HT) turnover was studied. Treatment with disulfiram caused increases in 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in rat brain. Under the same condition, activity of brain mitochondrial aldehyde dehydrogenase was reduced, however, supernatant aldehyde dehydrogenase and monoamine oxidase activities remained unchanged. Disulfiram had no effect on synthesis rate of 5-HT, but decreased metabolism of 5-HT. Moreover, disulfiram impaired transport of 5-HIAA from brain tissue.