The effects of insulin-treatment on induction of liver lipogenic enzymes by a fat-free diet were investigated in 1-, 2- and 9-month-old rats. The magnitudes of the induction of the enzymes were very high in 1-month-old rats and decreased with aging (Iritani, N., Fukuda, H. and Fukuda, E. (1981) Biochim. Biophys. Acta 665, 636). The induction of lipogenic enzymes was not affected by insulin injection in young rats. In 9-month-old rats, however, although the maximal magnitudes of the induction were not affected by the insulin injection, the lag periods of the induction were shortened. The lipogenic enzyme induction in 9-month-olds did not correlate with plasma insulin level but paralleled changes in the insulin binding capacities to liver plasma membranes and adipocytes. The results suggest that insulin binding is implicated in age-dependent decrease of lipogenic enzyme induction, and support our previous report (Iritani, N., Fukuda, H., Tashiro, S. and Ikeda, Y. (1982) J. Biochem. 92, 569).

Acetyl-CoA Carboxylase↗

PubMed1983

Anisatin modulation of temperature-dependent inhibition [3H]muscimol binding by chloride ion.

We investigated the effects of anisatin, a pure toxic substance isolated from Illicium anisatum, and chloride ion on [3H]muscimol binding to rat brain membranes at various temperatures (0-16 degrees C). Chloride ion (100 mM) itself slightly inhibited specific [3H]muscimol binding at 0-4 degrees C and this inhibition was more marked at 10 or 16 degrees C than at 0-4 degrees C. Anisatin further decreased [3H]muscimol binding inhibited by 100 mM chloride at 16 degrees C without affecting the basal specific binding. These effects of anisatin were also dependent on the temperature. Scatchard analysis revealed that the effects of chloride and chloride plus anisatin on [3H]muscimol binding were mainly due to reduction in the number of binding sites. The temperature- and chloride-dependent effects of anisatin were similar to those of picrotoxinin. Pre-treatment of membranes with 0.05% Triton X-100 markedly decreased the inhibitory effects of chloride and chloride plus anisatin. Our results indicate that anisatin affects the number of GABA receptor sites probably through the picrotoxin sensitive sites and that chloride ion not only modifies the GABA receptors but also plays an important role in the action of anisatin and picrotoxinin.

Animals↗

PubMed1983

Induction of rat liver malic enzyme messenger RNA activity by insulin and by fructose.

The effects of insulin treatment and fructose feeding on malic enzyme [EC 1.1.1.40] mRNA in liver of diabetic rats were investigated. A high fructose diet, even without insulin treatment, increased the mRNA activity, much more than a high starch diet, but to a lesser extent than insulin treatment. The increase of malic enzyme activity was approximately comparable to the change in mRNA activity, but occurred 12 hr and 30 hr after the increase of mRNA in the fructose-fed rats with and without insulin treatment, respectively. Thus, insulin and fructose appear to induce malic enzyme primarily by increasing the activity of translatable mRNA.

Animals↗

PubMed1983

Regulation by divalent cations of 3H-baclofen binding to GABAB sites in rat cerebellar membranes.

When investigating the effects of divalent cations (Mg2+, Ca2+, Sr2+, Ba2+, Mn2+ and Ni2+) on 3H-baclofen binding to rat cerebellar synaptic membranes, we found that the specific binding of 3H-baclofen was not only dependent on divalent cations, but was increased dose-dependently in the presence of these cations. The effects were in the following order of potency: Mn2+ congruent to Ni2+ greater than Mg2+ greater than Ca2+ greater than Sr2+ greater than Ba2+. Scatchard analysis of the binding data revealed a single component of the binding sites in the presence of 2.5 mM MgCl2, 2.5 mM CaCl2 or 0.3 mM MnCl2 whereas two components appeared in the presence of 2.5 mM MnCl2 or 1 mM NiCl2. In the former, divalent cations altered the apparent affinity (Kd) without affecting density of the binding sites (Bmax). In the latter, the high-affinity sites showed a higher affinity and lower density of the binding sites than did the single component of the former. As the maximal effects of four cations (Mg2+, Ca2+, Mn2+ and Ni2+) were not additive, there are probably common sites of action of these divalent cations. Among the ligands for GABAB sites, the affinity for (-), (+) and (+/-) baclofen, GABA and beta-phenyl GABA increased 2-6 fold in the presence of 2.5 mM MnCl2, in comparison with that in HEPES-buffered Krebs solution (containing 2.5 mM CaCl2 and 1.2 mM MgSO4), whereas that for muscimol was decreased to one-fifth. Thus, the affinity of GABAB sites for its ligands is probably regulated by divalent cations, through common sites of action.

Animals↗

PubMed1983

Experimental pancreas imaging study with 13N-glutamate using positron computer tomography.

Accumulation of 13N-L-glutamate in the pancreas was experimentally evaluated by tissue distribution studies and by positron computer tomography imaging studies. The pancreas and salivary gland of Donryu rats exhibited a high rate of 13N-glutamate uptake. The percent administered dose/g of pancreas was 3.8 at 20 min, 4.4 at 30 min after injection, and the pancreas to liver ratio was 1.9 and 2.5, respectively. The same results were obtained with Golden hamsters. The role of the feeding protocols was studied to optimize the technique. The fasting group showed a significantly higher uptake in the pancreas than in the free feeding group. The uptake in the fasting followed by a high protein meal group was higher than fasting only group, but the difference was not significant. Positron emission tomography of a miniature-pig with 13N-glutamate showed a clear image of the pancreas with the highest activity. It was concluded that 13N-glutamate was quite useful in positron imaging of the pancreas.

Animals↗

PubMed1983

Studies on 18F-labeled pyrimidines. Tumor uptakes of 18F-5-fluorouracil, 18F-5-fluorouridine, and 18F-5-fluorodeoxyuridine in animals.

Three 18F-labeled pyrimidines, 18F-5-fluorouridine (18F-5-FUR), 18F-5-fluorouracil (18F-5-FU), and 18F-5-fluorodeoxyuridine (18F-5-FdUR), were examined regarding tissue distribution and tumor uptake in ascitic hepatoma AH109A-bearing rats. The differential absorption ratios of tumors of 18F-5-FUR, 18F-5-FU, and 18F-5-FdUR were 0.75 +/- 0.21, 0.92 +/- 0.15, and 0.96 +/- 0.24 at 30 min, and 0.37 +/- 0.09, 0.64 +/- 0.34, and 0.60 +/- 0.17 at 120 min, respectively. The tumor-to-organ ratios obtained with three radiopharmaceuticals, especially with blood, heart, lung, muscle, and brain were high and these ratios increased with time. The tumor-to-organ ratios obtained with 18F-5-FdUR were always 1.3-4 times higher than 18F-5-FU and 18F-5-FUR. We concluded that 18F-5-FdUR was a suitable radiopharmaceutical for tumor imaging. Positron emission tomography of a rabbit tumor located on the chest with 18F-5-FdUR clearly showed the tumor within 1 h.

Animals↗

PubMed1983

Supersensitivity of the GABA receptor in the frog spinal cord, as induced by kainic acid.

In the isolated frog spinal cord perfused with kainic acid (KA, 5 X 10(-4) M) containing Ringer's solution, within 2 hr there were increases in the amplitude of the dorsal root depolarization, as induced by the GABA-agonists. KA perfusion produced increases in the specific binding of [3H]muscimol to crude synaptic membranes and incubation with KA for 3 hr did not increase [3H]muscimol binding. [3H]GABA was released from KA-treated spinal cord slices in the presence of high K+. KA-induced supersensitivity of the dorsal root to GABA may relate to direct actions on primary afferent terminals and not to denervation of GABAergic neurons.

Animals↗

PubMed1983

Sleep apnea and nocturnal myoclonus in elderly persons in Vilcabamba, Ecuador.

Four men (M age 90.5 years) and four women (M age 91.2 years) in Vilcabamba, Ecuador (a community noted for people with extreme longevity) volunteered for sleep recordings using four-channel Medilog portable cassette recorder. Of the eight physically healthy persons recorded, only one man displayed sleep apnea syndrome. No nocturnal myoclonus was observed. Low incidence of sleep apnea of elderly persons in Vilcabamba may be due to a low barometric pressure and/or lack of drug abuse.

Aged↗

PubMed1983

A consideration on histopathologic variability of diffuse pleural mesothelioma based on DNA cytophotometry.

Nuclear DNA cytophotometry of the tumor cells was performed for an autopsy case of malignant diffuse pleural mesothelioma diagnosed histologically as a mixed type. The DNA distribution of these tumor cells confirmed bimodality, one being situated in the triploid and the other in the pentaploid DNA range, thus indicating two stemline cell populations. In the former, the majority were epithelial mesothelioma cells resembling the normal mesothelial cells. The latter were mesenchymal tumor cells with spindle and occasionally bizarre shaped nuclei. This cytophotometric data strongly suggests that the histologic variability in mesotheliomas results probably from the change in number and ploidy level of the stemline cell population accompanied by neoplastic development.

Adult↗

PubMed1983

Effects of valproic acid on spinal reflexes and [3H]muscimol and [3H]diazepam binding in brain membranes in rats.

It was examined whether the anticonvulsant activity of valproic acid (di-n-propylacetic acid, DPA) was exerted via the inhibitory GABA system in the central nervous systems (CNS). Dorsal root reflexes (DR-DRR) were not augmented but intensely suppressed following the administration of DPA (50 and 200 mg/kg, i.v.). DPA did not depolarize the resting dorsal root potentials. These electrophysiological findings may indicate that DPA does not potentiate GABA system in the spinal cord of rats. DPA (1 and 10 mM) neither affected the binding of 2 or 40 nM of [3H]muscimol nor the binding of [3H]diazepam in the rat brain membranes; the same concentrations of DPA did not affect the enhancement of binding of [3H]diazepam induced by the addition of GABA (100 microM). The result obtained from binding assays indicates that DPA does not interact with the GABA-benzodiazepine receptor complex. The findings in the present study do not support the proposal that the anticonvulsant action of DPA is exerted by potentiation of the GABA system in the CNS.

Animals↗

PubMed1983

Anticonvulsant action of diazepam in mice pretreated with caffeine.

Anticonvulsant activities of diazepam in mice given pentylenetetrazol (PTZ), as well as effects of diazepam against potentiating activities of caffeine on these convulsions, were studied. Electroencephalographic (EEG) and electromyographic (EMG) recordings and behavioral observations were employed. First spike, clonic and tonic convulsions induced by PTZ were readily recognized from the EEG recording coupled with EMG recording. Pretreatment of mice with diazepam suppressed the incidence of clonic and tonic convulsions, but did not affect the development of first spike. These anticonvulsive effects of diazepam were also observed when PTZ-induced convulsions were potentiated with caffeine, except for clonic convulsion which was not suppressed with diazepam. The mechanisms of the antagonistic effects between diazepam and caffeine are discussed.

Animals↗