Effects of thiopental on regulatory mechanisms of brain energy metabolism

After administration of thiopental to artificially ventilated rats, the EEG, cerebral metabolism, intracellular distribution of hexokinase activity and the thiopental concentration in brain was measured. Considering the EEG changes, the time course of thiopental action was divided into an initial stage with increased beta activity and a following second stage with reduced beta activity. The glucose-6-phosphate concentration significantly increased in the first stage and fell again to the control level with the beginning of the second stage. Furthermore, during the second stage the glucose level increased and the hexokinase activity shifted from the mitochondrially bound form to the soluble form. From these results the following conclusions were drawn: Phosphofructokinase activity appeared inhibited only during the initial stage. During the second stage comparable to the stage of surgical anesthesia, thiopental solubilizes bound hexokinase activity inhibiting thereby energy metabolism.     

Effect of DL-butylphthalide (NBP) on mouse brain energy metabolism in complete brain ischemia induced by decapitation

The effects of NBP on gasping and brain energy metabolism after complete brain ischemia in mice subjected to decapitation were investigated. The levels of ATP, phosphocreatine (PCr) and lactate were determined by the method of Lowry. The data indicated that NBP at 112.5 or 250 mg.kg-1 sc can significantly prolong the duration of gasping and at the dose of 150 or 200 mg.kg-1 sc reduce the level of lactate and increase the levels of ATP and PCr after complete brain ischemia. The results suggest that NBP may have brain protective action and improve ischemic brain energy metabolism.     

Histamine metabolism and female sex hormones in women

Oral combined contraceptives did not seem to alter histamine metabolism in females. During treatment with gonadotrophic hormones in four amenorrhoeic patients there was a tendency towards increasing excretion of methylhistamine (MeHi) followed by a sudden decrease corresponding to changes in the urinary estrogen. The excretion of methylimidazoleacetic acid (MeImAA) seemed to parallel that of MeHi. The findings support the hypothesis that an endogenous surge of estrogen may influence histamine turnover in women. Women of post-menopausal age have about the same histamine metabolism as younger menstruating women. Estrogen medication relieved symptoms of hot flushes or sweats but did not seem to affect the histamine turnover.     

Short-term versus long-term effects of adrenal hormones on behaviors.

Hypothesizes that short-term exposures to stress facilitate performances of serially repetitive, overlearned tasks and impair performances of perceptual restructuring tasks, while long-term exposures to stress produce the opposite behavioral effects. These effects are attributed, in part, to the length of exposure of the central nervous system to stress-elicited adrenal hormones (epinephrine and cortisol). Short-term exposures are believed to induce states of central adrenergic dominance that favor performances of serially repetitive, overlearned tasks at the expense of perceptual restructuring tasks. Longer exposures are thought to result in a shift to central cholinergic dominance that favors the opposite pattern of performances. A physiological model is presented that accounts for the shift from central adrenergic to central cholinergic dominance. Experimental procedures derived from the model promote the reversal of some of the behavioral and physiological effects of a long-term stressor. (5 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of hyperglycemia on brain cell membrane function and energy metabolism during hypoxia-ischemia in newborn piglets

The purpose of this study was to test the hypothesis that hyperglycemia ameliorates changes in brain cell membrane function and preserves cerebral high energy phosphates during hypoxia-ischemia in newborn piglets. A total of 42 ventilated piglets were divided into 4 groups, normoglycemic/normoxic(group 1, n=9), hyperglycemic/normoxic(group 2, n=8), normoglycemic/hypoxic-ischemic(group 3, n=13) and hyperglycemic/hypoxic-ischemic(group 4, n=12) group. Cerebral hypoxia-ischemia was induced by occlusion of bilateral common carotid arteries and simultaneous breathing with 8% oxygen for 30 min. Hyperglycemia (blood glucose 350-400 mg/dl) was maintained for 90 min before and throughout hypoxia-ischemia using modified glucose clamp technique. Changes in cytochrome aa3 were continuously monitored using near infrared spectroscopy. Blood and CSF glucose and lactate were monitored. Na+, K+-ATPase activity, lipid peroxidation products (conjugated dienes), tissue high energy phosphates (ATP and phosphocreatine) levels and brain glucose and lactate levels were determined biochemically in the cerebral cortex. During hypoxia-ischemia, glucose levels in blood and CSF were significantly elevated in hyperglycemic/hypoxic-ischemic group compared with normoglycemic/hypoxic-ischemic group, but lactate levels in blood and CSF were not different between two groups. At the end of hypoxia-ischemia of group 3 and 4, triangle up Cyt aa3, Na+, K+-ATPase activity, ATP and phosphocreatine values in brain were significantly decreased compared with normoxic groups 1 and 2, but were not different between groups 3 and 4. Levels of conjugated dienes and brain lactate were significantly increased in groups 3 and 4 compared with groups 1 and 2, and were significantly elevated in group 4 than in group 3 (0.30+/-0.11 vs. 0.09+/-0.02 micromol g-1 protein, 26.4+/-7.6 vs. 13.1+/-2.6 mmol kg-1, p<0.05). These findings suggest that hyperglycemia does not reduce the changes in brain cell membrane function and does not preserve cerebral high energy phosphates during hypoxia-ischemia in newborn piglets. We speculate that hyperglycemia may be harmful during hypoxia-ischemia due to increased levels of lipid peroxidation in newborn piglet.     

Effect of photic stimulation on energy metabolism in the human brain measured by 31P-MR spectroscopy

Effect of photic stimulation (PS) on energy metabolism in the human occipital cortex was examined by using phosphorus-31 magnetic resonance spectroscopy in 9 normal subjects. Phosphocreatine (PCr)/total phosphorus signal peak area ratio significantly decreased from 12.3% to 10.9% during the 12 minutes of PS (P < 0.05). PCr once returned to a normal level after PS (11.9%) but significantly decreased again 12-18 minutes after PS (10.8%; P < 0.05). Intracellular pH increased from 7.08 to 7.16 during PS, although this increase was not significant. These results suggest that functional alteration of energy metabolism in the brain is different from that in muscles.     

Steroid hormones and their receptors in the brain

Steroid hormones regulate several important functions of the brain by altering the expression of particular genes through their receptors. First in this paper the localization of glucocorticoid receptor immunoreactivity and mRNA in the brain was examined. Second biphasic effects of glucocorticoid on the hippocampus was described and particular emphasis was given on the apoptosis. Third the significance of estrogen receptor in the sexually dimorphic areas was discussed. These results suggest that steroids modulate the gene expression along with the alteration of cell structures in a different manner in a tissue-specific pattern.     

Effects and metabolism of steroid hormones in human neuroblastoma cells

The development of the central nervous system is influenced by sex steroids and by their metabolites. However, little information on the possible effects of steroid hormones on neuroblastoma cells is available. Human neuroblastoma cell lines have been used as a model of human neuroblasts in vitro to study the metabolism of steroid hormones; in addition, the effects of steroids and steroid antagonists on neuroblastoma cell growth have also been investigated. The results obtained show that SH-SY5Y human neuroblastoma cells may actively metabolize testosterone and progesterone to their respective 5 alpha-reduced metabolites and that differentiation of neuroblastoma cells is paralleled by a significant increase in expression of the type-1 5 alpha-reductase and of the formation of steroid metabolites. All these data are suggestive of a potential role of steroid 5 alpha-reduced metabolites in the biology of neuroblastoma cells. Studies performed to analyze the role of steroid hormones on neuroblastoma cell proliferation show that progesterone at low doses may induce minor stimulation, and at higher doses, a toxic effect on the neuroblastoma cell line SK-N-SH is seen. Moreover, the antiprogestin 17 beta-hydroxy-11 beta-(4-dimethylamino-phenyl-1)-17-(prop-1-ynyl)estra-4,9-dien+ ++-3-one (RU486) decreases the proliferation of these cells in a dose-dependent manner. The effect of RU486 is not antagonized by either progesterone or dexamethasone, a result that seems to exclude the action of RU486 via classic intracellular steroid hormone receptors.     

Tetrahydroisoquinolinecarboxylic acids and catecholamine metabolism in adrenal medulla explants

In a study of the relationship of the tetrahydroisoquinolinecarboxylic acids (TIQCAs) to catecholamine metabolism, we have investigated their effects on cultured rat adrenal medulla explants. Medullae were incubated in medium containing norlaudanosolinecarboxylic acid (NLCA) or 3',4'-deoxynorlaudanosolinecarboxylic acid (DNLCA) (0.5 mM) in the presence and absence of [3H]tyrosine. By paired-ion reverse-phase high pressure liquid chromatography, tissue epinephrine (EPI), norepinephrine (NE), dopamine (DA) and TIQCA were resolved. Endogenous concentrations were measured with electrochemical detection, and radioactivity was assayed by collecting appropriate effluents. Tissue levels of the TIQCAs reached saturating levels of 0.36 mM by about 20 hr. DNLCA elicited a significant decrease (60%) in endogenous DA, NE and EPI at 40 hr, whereas only DA was depressed at 30 hr. NLCA had little effect after 30 or 40 hr. When tissues were maintained in the presence of alpha-methyltyrosine (0.5 mM) for 40 hr, catecholamine levels were depressed to an extent similar to that observed with DNLCA. Incubation with [3H]tyrosine in the presence of TIQCAs revealed inhibition of tyrosine uptake and suggested a reduction in the rate of catecholamine synthesis. These results are consistent with previous data on the inhibition of tyrosine 3-monooxygenase by DNLCA in vitro.     

Strain differences in adrenal microsomal steroid metabolism in guinea pigs

We recently reported that CYP2D16, a xenobiotic-metabolizing P450 isozyme, was expressed at higher levels in adrenal microsomes from inbred Strain 13 guinea pigs than in those from outbred English Short Hair (ESH) animals. Studies were done to determine if there also were strain differences in adrenal microsomal steroid metabolism. In both inner (zona reticularis) and outer (zona fasciculata plus zona glomerulosa) zone preparations of the adrenal cortex, 21-hydroxylase activities were greater in microsomes from ESH than from Strain 13 guinea pigs. By contrast, 17alpha-hydroxylase activities were similar in the two strains. In both strains, 21-hydroxylase activities were greater in inner than outer zone microsomes, but the opposite was found for 17alpha-hydroxylase activities (outer>inner). Northern and Western analyses revealed higher levels of CYP21 mRNA and protein in adrenals from ESH than Strain 13 guinea pigs, but there were no strain differences in CYP17 mRNA or protein concentrations. Despite the zonal differences in adrenal 17alpha-hydroxylase and 21-hydroxylase activities, CYP17 and CYP21 mRNA and protein levels were similar in the inner and outer zones within each strain of guinea pig. The results demonstrate strain differences in microsomal steroid metabolism that are explained by differences in CYP21 expression. By contrast, the zonal differences in steroid hydroxylase activities may be attributable to post-translational mechanisms.     

Uptake and metabolism of serotonin by rat adrenal tissue in vitro

After incubation of separate zones of rat adrenals with radioactively labelled serotonin--at concentrations at which the amine had been previously shown to stimulate aldosterone biosynthesis--the tissue radioactivity was several times higher in the capsular ("zona glomerulosa") than in the decapsulated portions of the glands. High doses of unlabelled serotonin diminished the accumulation of radioactivity, but only when added simultaneously with the tracer. In the course of the incubation, radioactive 5-hydroxy-3-indoleacetic acid, i.e. the deaminated metabolite of serotonin, rapidly appeared in the medium. Most of the radioactive material accumulated by the adrenal was recovered in the cytosol fraction and was no longer identical with serotonin, but consisted mainly of 5-hydroxy-3-indoleacetic acid and another, unidentified metabolite. Unaltered serotonin was found in capsular adrenal tissue extracts only when a monoamine oxidase inhibitor (nialamide) has been added to the incubation medium. Rapid uptake and metabolism thus appeared to be the predominant features of the interaction of incubated adrenal tissue with serotonin. These events may have obscured the possible binding of very small amounts of serotonin to receptor sites. The observed accumulation of radioactivity in adrenal tissue was mainly due to delayed outflow of intracellulary formed metabolite, since 5-hydroxy-3indoleacetic acid was neither taken up by incubated adreanls nor bound by adrenal cytosol. No evidence of serotonin storage in the zona glomerulosa was found in these studies.     

Further studies on the role of the adrenal hormones in responses of rats to meal-feeding

The importance of the adrenal hormones in the lipogenic responses to meal-feeding or starvation-refeeding was studied. In experiment 1, intact or adrenalectomized (ADX) rats were either ad libitum-fed or meal-fed a 65% glucose diet for 21 days or until moribund (ADX rats only). Serum glucose and electrolytes (Ca++, Mg++, Na+, K+), hepatic glycogen and glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme (ME) were determined. ADX rats died within 10 days after the initiation of meal-feeding and were hypoglycemic with low liver glycogen levels and low enzyme activities. No differences in serum electrolytes were observed. In the second experiment, ADX and intact rats of varying initial weights were weight paired and meal-fed. When the ADX rat died, his intact control was killed and both carcasses assayed for fat content. Heavier rats with presumably more carcass fat survived meal-feeding longer than the lighter rats. Rats died when they had lost all but 2 to 3 g carcass lipid. In experiments 3 and 4, ADX and intact rats were subjected to starvation-refeeding. In experiment 4, additional ADX groups were given supplemental doses of cortisol (0.75 mg/kg, subcutaneous, 2 times daily) during either the starvation period, the refeeding period or during both periods. The activities of hepatic G6PD and ME were determined as well as the levels of liver lipid in experiment 4. Intact starved-refed rats had the usual enzyme overshoot, whereas ADX starved-refed rats did not. Cortisol-treated ADX starved-refed rats had as great an enzyme overshoot as the intact rats and as great an increase in liver lipid. These results suggest that ADX rats die when meal-fed the glucose diet, because they are unable to store sufficient metabolic fuel for use during the starvation phase of the meal-feeding cycle. Further, the results show that glucocorticoids are required for the induction of de novo enzyme synthesis.