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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of vagal inhibitory stimulation and of purine compounds were studied in the rabbit stomach. 2. Gastric motility was assessed by the balloon method. Vagal nerves were electrically stimulated at the neck. Purine compounds were injected intra-arterially. 3. In the atropine-treated rabbit, vagal stimulation caused relaxant motor responses followed by a rebound contraction. 4. Among the purine compounds, only ADP and ATP caused relaxant motor responses similar to the effects of vagal inhibitory stimulation. However, the relaxation produced by ATP was more powerful than that due to ADP, especially at lower infusion rates. 5. Vagal inhibitory responses were recorded during and after infusion of ATP. When relaxation by ATP was fully developed, vagal inhibitory stimulation was ineffective. At the highest infusion rates of ATP, a depression of the vagal inhibitory motility was also observed after cessation of the infusion. 6. Relaxant responses to ATP and vagal inhibitory stimulation were not influenced by theophylline, scarcely affected by alpha,beta-methylene ATP, but were reduced or blocked by reactive blue 2. 7. The results are consistent with ATP being an inhibitory neurotransmitter in the stomach of the rabbit.
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PMID:Gastric motor responses elicited by vagal stimulation and purine compounds in the atropine-treated rabbit. 320 79

Inhibition of ADP phosphorylation by both glycolysis and mitochondria in P388D1 cells exposed to H2O2 is described. Net glucose uptake and lactate production were inhibited by oxidant exposure (ED50 = 50-100 microM). Glycolysis was specifically inactivated at the glyceraldehyde-3-phosphate dehydrogenase step by three independent mechanisms: (a) direct inactivation of the intracellular enzyme (ED50 approximately equal to 100 microM); (b) reduction of the intracellular concentration and redox potential of its nicotinamide cofactors; and (c) a cytosolic pH shift further from the enzyme optima. Consistent with inhibition of glycolysis at the glyceraldehyde-3-phosphate dehydrogenase step, a rise in the intracellular concentration of glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, and fructose 1,6-bisphosphate was observed. The calculated combined inhibition of glyceraldehyde-3-phosphate dehydrogenase activity could be reasonably correlated with the depression in glycolytic flux rate with the appropriate modeling. The steady-state contribution by mitochondria to the total intracellular ATP pool was indirectly determined by the use of various metabolic inhibitors and was found to rapidly decline following exposure to 300-800 microM H2O2. The inhibition of ADP phosphorylation appeared to be related more to the direct inhibition of the ATPase-synthase complex rather than to the diminished capacity of the respiratory chain for coupled electron transport. Both the estimated rates of ADP phosphorylation by glycolysis and mitochondria and the estimated rate of ATP hydrolysis by ongoing metabolism were utilized to model the approximate decline in intracellular ATP expected at 15-min exposure to various H2O2 concentrations. Theoretical calculations and the measured intracellular ATP status were in good agreement. Oxidant exposure for 15 min resulted in dose-dependent killing of the cells (ED50 = 500 microM), indicating a close correlation between H2O2-mediated loss of intracellular ATP and cell viability. The possible contribution of impaired energy homeostasis during oxidant-mediated injury to the process of cell dysfunction and death is discussed.
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PMID:Mechanisms of oxidant-mediated cell injury. The glycolytic and mitochondrial pathways of ADP phosphorylation are major intracellular targets inactivated by hydrogen peroxide. 333 86

Serotonin content and accumulation in platelets and its release from them, as well as changes in thrombus formation in mesenteric arterioles and venules of the small intestine have been investigated in control rats and rats with spontaneous hypertension (SHR). Serotonin accumulation in platelets was determined upon its incubation with platelets. Disodium ADP salt was used as an inductor of release. Laser-induced thrombosis was caused by microvessels exposure to impulse laser irradiation. The control animals revealed a significant difference between the initial serotonin platelet level and serotonin level upon incubation and release; in values, the values of basic thrombus-forming parameters were higher than in arterioles. In SHR there is a decrease in biogenic amine content in platelets, a depression in its accumulation and release, an increase in the time of thrombus growth, its size up to the separation of the first embolus and its length along the vascular wall. It is concluded that spontaneous hypertension is characterized by decreased functional activity of platelets and depressed resistance of arterioles and venules to thrombus formation.
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PMID:[Serotonin metabolism in thrombocytes and microvascular hemostasis in spontaneous arterial hypertension]. 334 66

To delineate the active free radical species mediating the toxic effects of autoxidizing dihydroxyfumarate (DHF), isolated rabbit right ventricular papillary muscles were exposed to 4.5 mM DHF in the presence of FeCl3, ADP and bovine albumin. In the absence of free radical scavengers a 47.3 +/- 11.5% (mean +/- standard deviation) depression in contractile force was noted over 60 minutes. Neither the combination of superoxide dismutase (SOD) 3,200 u/cc and catalase (CAT) 2,950 u/cc nor mannitol 0.1 M provided statistically significant protection. Deferoxamine mesylate (DFX) 10 mg/cc (15 mM) did provide significant protection of muscle function both in the presence and absence of SOD and CAT (p less than 0.01). The degree of protection conferred by DFX alone was statistically similar to that of DFX with SOD and CAT. This data suggests the involvement of an iron-oxygen complex not dependent on superoxide or hydrogen peroxide for its formation and not readily scavenged by mannitol. The perferryl ion may be representative of such a species. Alternatively, a reactive complex similar to the 'Crypto-OH' radical proposed by Youngman may be formed by the reaction of DHF with iron and oxygen.
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PMID:The effects of dihydroxyfumarate on isolated rabbit papillary muscle function: evidence for an iron dependent non-hydroxyl radical mechanism. 344 Dec 52

The protective effect of prostaglandins (PGs) against cerebral hypoxia/anoxia was investigated with a variety of experimental models in relation to their CNS depressant effects in mice. Furthermore, the effect of PGs on the changes of cerebral energy metabolites and cyclic nucleotide was examined in hypoxic mice. Mice were given s.c. doses of PGs 30 min before tests. Among the PGs tested, treatment with PGD2, PGE1 and PGI2 Na showed a consistent and dose-dependent protection against cerebral anoxia induced by all models studied: histotoxic anoxia by KCN, hypobaric hypoxia, normobaric hypoxia and decapitation-induced gasping. However, PGA1, PGA2, PGB1, PGB2, PGE2, PGF1 alpha, PGF2 alpha and 6-keto-PGF1 alpha at a dose of 3 mg/kg were without effect against normobaric hypoxia and gasping duration. The three PGs, i.e. PGD2, PGE1 and PGI2 which showed anti-hypoxic effects decreased locomotor activity and potentiated hexobarbital-induced sleep. On the other hand, PGE2, PGA1, PGA2 and PGB2 also caused a decrease in locomotor activity. Similarly, PGE2 and PGA1 caused a potentiation of hexobarbital-induced sleep, but interestingly they did not cause clear-cut increase in cerebral resistance to hypoxia, in contrast with the former three PGs. Thus general depression of CNS function appears not to be responsible for the PGD2-, PGE1- and PGI2-induced increase in cerebral resistance to hypoxia. The levels of Cr-P and ATP were significantly reduced and those of ADP and AMP were markedly elevated in hypoxic brain, resulting in a decrease in a calculated energy charge potential. The lactate level and lactate/pyruvate ratio increased and the glucose level decreased markedly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effect of prostaglandins D2, E1 and I2 against cerebral hypoxia/anoxia in mice. 354 99

General pharmacological properties of isepamicin sulfate (HAPA-B), a new aminoglycoside antibiotic, were studied in animals and the results obtained were summarized below. Intramuscular injections of HAPA-B at doses of 500 mg/kg inhibited the writing response induced by acetic acid, and at doses of 1,000 mg/kg, caused muscle relaxation, respiratory depression, suppression of spontaneous motor activity and prolongation of thiopental anesthesia. Anticonvulsive action and the effect on the rectal temperature were not observed. Intravenous Intravenous HAPA-B showed no significant effect on the general behavior and the function of the central nervous system at doses of 100 mg/kg. Intravenous injections of HAPA-B to anesthetized dogs resulted increases in the femoral arterial blood flow at doses of 12.5 mg/kg, decrease in the blood pressure and increase in the respiratory rate at doses of 25 mg/kg, and increase in the carotid arterial blood flow at doses of 50 mg/kg. Apparent changes were not recognized in the heart rate and electrocardiograms. In conscious rabbits, intravenous HAPA-B produced increases in the heart rate without significant changes of the blood pressure and electrocardiograms at doses of 100 mg/kg. Spontaneous beatings of isolated atria were depressed by HAPA-B in concentrations of 3 X 10(-4) to 10(-3) g/ml. The HAPA-B inhibited the gastric secretion at intramuscular doses of 500 mg/kg or intravenous doses of 100 mg/kg, and depressed charcoal transport through small intestine and the spontaneous movement of isolated ileum at intramuscular doses of 1,000 mg/kg and at concentrations of 3 X 10(-4) to 10(-3) g/ml, respectively. No irritative effect was found on the gastric mucous membrane. Intravenous HAPA-B inhibited the response of nictitating membrane to pre and post ganglionic stimulations of cervical sympathetic nerve at doses of 100 mg/kg. In in vitro test, HAPA-B inhibited nonspecifically the constrictive responses of trachea, aorta, stomach, ileum and vas deferens to various agonists in concentrations of 3 X 10(-4) to 10(-3) g/ml. Spontaneous movements of uteri of estrous or pregnant animals were depressed by HAPA-B at intravenous doses of 50 to 100 mg/kg and in in vitro at concentrations of 10(-4) to 3 X 10(-4) g/ml. Antidiuretic effect was also observed at intramuscular doses of 250 mg/kg. HAPA-B increased the length of the whole blood clotting time and raised the plasma glucose level at intramuscular doses of 1,000 mg/kg and inhibited the platelet aggregation induced by ADP in vitro at concentrations of 10(-3) g/ml.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[General pharmacological studies on isepamicin sulfate (HAPA-B)]. 358 27

The effect of asphyxia and subsequent resumption of respiration on the content of adenine nucleotides and some amino acids in heart tissue and mitochondria, as well as respiration of heart mitochondria was studied in rats. The depression of cardiac contractile function during asphyxia showed a better correlation with losses in mitochondrial adenine nucleotides (ATP + ADP + AMP) than those in cardiac tissue. The decrease in the heart work index was accompanied by a decrease in state 3 respiration with glutamate and malate as well as uncoupled respiration with these substrates. This did not occur with succinate. Nonphosphorylating (state 4) respiratory rates and ADP/O ratios were slightly affected by asphyxia, when respiratory substrates of both types were used. The decreased level of glutamic acid in the tissue and mitochondria of asphyxic hearts was simultaneously observed with a significant increase of alanine in cardiac tissue and of aspartic acid in the mitochondria. The losses of intramitochondrial ATP and respiratory activity with NAD-dependent substrates during asphyxia were associated with a reduction of glutamic acid level in mitochondria. The recovery of cardiac function during resumption of respiration was related to the restoration of mitochondrial respiration supported by glutamate and malate, as well as to the restoration of mitochondrial adenine nucleotides and glutamic acid. The results suggest that the depression of cardiac function caused by acute respiratory hypoxia may be attributed to impairment of electron transport, particularly in complex I of the respiratory chain and changes in metabolism of glutamic acid.
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PMID:The relationship between the cardiac contractile function, adenine nucleotides and amino acids of cardiac tissue and mitochondria at acute respiratory hypoxia. 361 64

The oxidation of pyruvate is mediated by the pyruvate dehydrogenase complex (PDHC; EC 1.2.4.1, EC 2.3.1.12 and EC 1.6.4.3) whose catalytic activity is influenced by phosphorylation and by product inhibition. 2-Oxoglutarate and 3-hydroxybutyrate are readily utilized by brain mitochondria and inhibit pyruvate oxidation. To further elucidate the regulatory behavior of brain PDHC, the effects of 2-oxoglutarate and 3-hydroxybutyrate on the flux of PDHC (as determined by [1-14C]pyruvate decarboxylation) and the activation (phosphorylation) state of PDHC were determined in isolated, non-synaptic cerebro-cortical mitochondria in the presence or absence of added adenine nucleotides (ADP or ATP). [1-14C]Pyruvate decarboxylation by these mitochondria is consistently depressed by either 3-hydroxybutyrate or 2-oxoglutarate in the presence of ADP when mitochondrial respiration is stimulated. In the presence of exogenous ADP, 3-hydroxybutyrate inhibits pyruvate oxidation mainly through the phosphorylation of PDHC, since the reduction of the PDHC flux parallels the depression of PDHC activation state under these conditions. On the other hand, in addition to the phosphorylation of PDHC, 2-oxoglutarate may also regulate pyruvate oxidation by product inhibition of PDHC in the presence of 0.5 mM pyruvate plus ADP or 5 mM pyruvate alone. This conclusion is based upon the observation that 2-oxoglutarate inhibits [1-14C]pyruvate decarboxylation to a much greater extent than that predicted from the PDHC activation state (i.e. catalytic capacity) alone. In conjunction with the results from our previous study (Lai, J. C. K. and Sheu, K.-F. R. (1985) J. Neurochem. 45, 1861-1868), the data of the present study are consistent with the notion that the relative importance of the various mechanisms that regulate brain and peripheral tissue PDHCs shows interesting differences.
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PMID:The effect of 2-oxoglutarate or 3-hydroxybutyrate on pyruvate dehydrogenase complex in isolated cerebrocortical mitochondria. 362 60

The biochemical mechanism of acute contractile failure in the hypoxic rat heart was investigated using phosphorus nuclear magnetic resonance to measure intracellular acidosis and the concentrations of phosphocreatine, adenosine triphosphate (ATP), and inorganic phosphate while cardiac mechanical function was simultaneously monitored. The cytosolic free [ADP] was calculated from the creatine kinase equilibrium expression. Mechanical activity, phosphocreatine and ATP concentrations, and intracellular pH all decreased after the onset of hypoxic perfusion. Neither a reduction in ATP concentration nor limitation in its rate of production contributed to the early contractile failure. Calculations suggest only a modest (approximately 10%) difference in cytosolic free energies of ATP hydrolysis. Neither the time course nor the extent of depression of mechanical function correlated well with intracellular acidosis. In conjunction with other observations, these results were consistent with the view that the myocardial inotropic state may be directly responsive to the ambient PO2. The overall rate of ATP turnover was assessed from measurements of oxygen utilisation and lactate production in both normoxic and hypoxic hearts. Surprisingly, despite more than an 80% reduction in mechanical activity during hypoxia, no significant decrease in the rate of ATP utilisation was noted during hypoxia. This suggests that unidentified non-contractile processes may hydrolyse ATP at relatively higher rates during hypoxia.
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PMID:Biochemical mechanisms of acute contractile failure in the hypoxic rat heart. 370 37

The effect of acute hypoxia on adenine nucleotides, glutamate, aspartate, alanine and respiration of heart mitochondria was studied in rats. The losses of intramitochondrial adenine nucleotides (ATP+ADP+AMP) during hypoxia were related to depression of state 3 respiration supported by glutamate and malate, as well as decrease in uncoupled respiration. Hypoxia had less prominent effect on succinate-dependent state 3 respiration. Non-phosphorylating (state 4) respiratory rates and ADP/O ratios were slightly affected by oxygen deprivation. Glutamate fall in tissue and mitochondria of hypoxic hearts was concomitant with significant increase in tissue alanine and mitochondrial aspartate. The losses of intramitochondrial ATP and respiratory activity with NAD-dependent substrates during hypoxia were related to a decrease in mitochondrial glutamate. The results suggest that hypoxia-induced impairment of complex I of respiratory chain and a loss of glutamate from the matrix may limit energy-producing capacity of heart mitochondria.
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PMID:Adenine nucleotides, glutamate and respiratory function of heart mitochondria during acute hypoxia. 375 8


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