Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effect of dietary essential fatty acid (EFA) deficiency on Ca(2+)-ATPase activity of rat submandibular gland microsomal fraction was studied. 2. The specific activity of Ca(2+)-ATPase per milligram of microsomal protein was depressed about 35% in rats fed the EFA-deficient diet as compared with that in those fed the control diet. 3. Lineweaver-Burk plots for Ca(2+)-ATPase activity showed no significant differences in Km values for Ca2+ and ATP, but the Vmax was decreased in the EFA-deficient rats. 4. The above results suggest that depression of the Ca(2+)-ATPase activity in rats fed the EFA-deficient diet is probably due to the decrease in the Vmax of the enzyme.
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PMID:Effect of dietary essential fatty acid deficiency on Ca(2+)-ATPase activity in microsomal fraction of rat submandibular gland. 183 78

Oral administration of the antiulcerogenic drug, cimetidine, was studied on kidney-bound hydrolytic enzymes at three different dose levels (30 mg, 100 mg, and 2000 mg/kg body weight) and for single administration for 2 and 24 h, and daily administration for 15 days in mice. It significantly inhibited Na+, K(+)-ATPase, Mg(2+)-ATPase, and Ca2+, Mg(2+)-ATPase in the isolated basolateral membrane (BLM). Brush-border-membrane-(BBM)-associated enzymes, sucrase, lactase, maltase, leucine aminopeptidase, and alkaline phosphatase also showed a marked reduction. Substrate saturation kinetics revealed the nature of inhibition was of mixed type in the case of sucrase, lactase, maltase, and alkaline phosphatase (Km was increased, while Vmax decreased), whereas it was of non-competitive type for leucine aminopeptidase (Km was unchanged, while Vmax decreased). In vitro addition of cimetidine (5-20 mM) to the BBM also inhibited the enzyme activity. Dixon plot produced the inhibition constant (Ki) for cimetidine in the case of maltase, alkaline phosphatase, and leucine aminopeptidase in the order of 14.83, 32.83 and 11.5 mM, respectively. Analysis of lipids revealed a significant reduction in BBM-associated phospholipid and phospholipid/cholesterol molar ratio, while the neutral lipid fraction, i.e., cholesterol and triglycerides were not altered. Free fatty acid exhibited an increase after drug treatment, which was significant at higher dose after 24 h of single and 15 days of daily treatment. BLM-associated lipids did not exhibit any significant change. Cimetidine-induced depression in renal BLM- and BBM-associated disaccharidases and ATPases, at least at the higher dose level, may have serious consequences in the absorption of end-product nutrients.
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PMID:Depression of membrane-bound hydrolases by cimetidine in mouse renal basolateral and brush border. 183 34

Sarcoplasmic reticulum (SR) isolated from the deep red portion of the gastrocnemius muscle of Sprague-Dawley rats after a single bout of prolonged exercise was shown to have depressed Ca(2+)-stimulated Mg(2+)-dependent ATPase activity over a temperature range of 15 to 42.5 degrees C when compared to SR obtained from control muscle. Inclusion of the calcium ionophore, A23187, failed to restore the depressed ATPase activity from SR of exercised muscle to control values, but it did normalize the stimulatory effect of temperature on ATPase activity. This depression was also manifested as an increased activation energy when the data were converted to an Arrhenius plot. SR vesicles from both groups showed no differences or discontinuities in plots of steady-state fluorescence anisotropy. When the binding characteristics of the fluorescent probe, fluorescein isothiocyanate (FITC), were analyzed, SR vesicles prepared from exercised muscle displayed a 40% reduction in binding capacity with no apparent change in Kd. These findings support the conclusion that a single bout of exercise induces a structural change in the Ca(2+)-ATPase protein of rat red gastrocnemius muscle that is not a direct result of gross lipid alterations or increased muscle temperature.
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PMID:Prolonged exercise induces structural changes in SR Ca(2+)-ATPase of rat muscle. 183 29

1. Gastrin (G)-cell function is controlled by gastric acid, which has inhibitory effects, and food in the gastric lumen, which has stimulatory effects. We have examined the role of acid in mediating the depression of G-cell function that occurs in fasting in the rat. 2. Rats were fasted for 48 h, and received either the H(+)-K(+)-ATPase inhibitor omeprazole, to reduce acid secretion, or vehicle. Basal acid secretion was not significantly different after fasting for 24 or 48 h. Fasted rats which received omeprazole were achlorhydric. 3. In rats treated with vehicle and fasted for 48 h, plasma and tissue gastrin concentrations were significantly depressed. The fall in both parameters suggests an inhibition of gastrin synthesis and consistent with this a decrease was observed in tissue gastrin mRNA abundance and in phosphorylation of progastrin-derived peptides. 4. In fasted rats treated with omeprazole, tissue gastrin concentrations were not significantly different from those of rats fed ad libitum, but plasma gastrin concentrations were significantly higher than in rats fed ad libitum. Gastrin mRNA abundance and the phosphorylation of progastrin-derived peptides in omeprazole-treated rats was not significantly different from rats fed ad libitum. 5. The data suggest that the depression of G-cell function which occurs in fasted rats can be attributed to the inhibitory action of intraluminal acid on the G-cell. Gastric acid appears to regulate several different aspects of G-cell function, including gastrin synthesis, post-translational processing and secretion.
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PMID:Reversal by omeprazole of the depression of gastrin cell function by fasting in the rat. 184 54

Addition of bovine serum albumin to state 4 mitochondria results in a depression of the proton leak and of the resting respiration of 70 and 25%, respectively. The conductance membrane potential diagram, both in the ohmic and in the non-ohmic region, shows that in the presence of bovine serum albumin the level of ohmic conductance is lowered while that of non-ohmic conductance is increased toward higher delta psi values. The same effect is observed during operation of the different proton pumps. Addition of chloroform affects the conductance membrane potential diagram in the following manner: there is no effect in the ohmic region with all pumps, while there is an effect in the non-ohmic region either at site III or at sites II plus III but not at site II. This suggests a possible effect of chloroform at the level of the cytochrome oxidase proton pump. During titration with oligomycin of the ATPase proton pump the conductance potential diagram shows a region of non-ohmicity only in the presence but not in the absence of an ATP-regenerating system. Protonophoric uncouplers such as carbonyl cyanide p(trifluoromethoxy)phenylhydrazone and intrinsic uncouplers such as chloroform have different effects on the relationship between rates of charge translocation and of oxygen consumption, and thus on the pump stoichiometries, in that the slope of the diagram is modified by the latter but not by the former. The differential effects of protonophores and of intrinsic uncouplers on the stoichiometries have been analyzed by computer simulations and represent an additional criterion to distinguish between extrinsic and intrinsic mechanisms of uncoupling.
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PMID:Flux ratios and pump stoichiometries at sites II and III in liver mitochondria. Effect of slips and leaks. 184 85

In order to understand the role of carnitine metabolites in the genesis of cellular dysfunction and damage due to myocardial ischemia, the effects of 1-100 microM L-carnitine, acetylcarnitine, propionylcarnitine, and palmitoylcarnitine were investigated on rat heart sarcolemmal, sarcoplasmic reticular, and mitochondrial ATPase activities. Palmitoylcarnitine, unlike acetylcarnitine, propionylcarnitine and carnitine, produced marked inhibitory actions on sarcolemmal Na,K-ATPase and Ca2(+)-stimulated ATPase, as well as sarcoplasmic reticular Ca2(+)-stimulated ATPase activities; Na,K-ATPase was most sensitive. Although palmitoylcarnitine, unlike carnitine or its short-chain fatty-acid derivatives, also depressed sarcolemmal Ca2+ ATPase or Mg2+ ATPase, sarcoplasmic reticular Mg2+ ATPase, and mitochondrial Mg2+ ATPase, mitochondria were less sensitive in comparison to other organelles. Myofibrillar Ca2(+)-stimulated ATPase was slightly inhibited by very high concentrations of palmitoylcarnitine only. It is suggested that the observed depression of the sarcolemmal Na(+)-pump system by low concentrations of long-chain acyl derivatives of carnitine may contribute towards the pathogenesis of arrhythmias due to myocardial ischemia. Furthermore, the inhibition of Ca2(+)-pump mechanisms in the sarcolemmal and sarcoplasmic reticular membranes by relatively high concentrations of palmitoylcarnitine may result in the occurrence of intracellular Ca2+ overload and subsequent cell damage, as well as cardiac dysfunction due to myocardial ischemia.
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PMID:Effects of some L-carnitine derivatives on heart membrane ATPases. 185 32

Epidemiologic studies have shown that insulin is a risk factor for coronary heart disease (CHD). Clinical studies have also demonstrated positive correlations between insulin and blood pressure, triglycerides, total cholesterol, fibrinogen, and plasminogen activator inhibitor. Moreover, there is an inverse correlation between insulin and high-density lipoprotein (HDL). These studies have provided evidence in support of the biologic plausibility of epidemiologic observations, but they have not clearly established insulin's role in the pathogenesis of human cardiovascular diseases (CVD) such as hypertension. In fact, there is considerable evidence that insulin resistance (abnormal nonoxidative glucose disposal), not hyperinsulinemia, is the primary insulin-related abnormality in human hypertension, and that hyperinsulinemia occurs as a response to insulin resistance. Skeletal muscle appears to be the primary site of insulin resistance in essential hypertension, although other organs, such as the kidneys and liver--key sites for cell and water homeostasis and lipoprotein regulation, respectively--may respond normally to insulin. Adipocytes also appear to be a site of insulin resistance. Thus, the putative interrelationship between hyperinsulinemia and insulin resistance, on the one hand, and with blood pressure and lipoproteins, on the other, is a complex one and may involve organ-specific insulin resistance. Altered cation transport is one of several mechanisms by which insulin resistance might raise blood pressure. The Na+, K(+)-ATPase and Ca(2+)-ATPase pumps are insulin sensitive. Thus, when insulin resistance is present, the activity of these pumps in the smooth muscle of the arterial wall might be reduced. This would lead to an intracellular accumulation of sodium and calcium, thereby sensitizing the vascular wall to pressor substances. Moreover, secondary hyperinsulinemia will occur, and insulin has been shown to stimulate sympathetic nervous system activity and to increase renal tubular absorption of sodium. Insulin is also a growth factor and therefore might have a trophic effect on the vessel wall, one that could initiate and/or sustain hypertension as well as atherosclerosis. Abnormal lipoprotein metabolism is yet another possible explanation for the accelerated atherosclerosis that has been observed in persons with abnormal carbohydrate tolerance and insulin resistance. Hyperinsulinemia and insulin resistance both play a role in the expression of elevated very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels as well as in the depression of HDL levels. Coronary risk reduction has been disappointing when blood pressure has been lowered with treatment regimens based on thiazide diuretics and/or beta blockers. Thiazides and some beta blockers may further impair tissue insulin sensitivity and often cause blood lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia. 186 24

Oxygen free radicals have been implicated as mediators of cellular injury in ischemia-reperfusion. Since intracellular Ca(2+)-overload has been considered to play a crucial role in ischemia-reperfusion injury, this study was undertaken to examine the effects of oxygen free radicals on Ca(2+)-stimulated Mg(2+)-dependent ATPase activities and ATP-dependent Ca2+ accumulation in rat cardiac sarcolemmal membranes in vitro. Isolated rat heart sarcolemmal membranes were incubated with xanthine (X) + xanthine oxidase (XO) and assayed for Ca(2+)-pump activities. X + XO inhibited the Ca(2+)-pump activities in a time-dependent manner; a significant inhibition of Ca(2+)-stimulated ATPase activity was seen after one min of incubation. Superoxide dismutase showed a protective effect on depression in Ca(2+)-pump activities due to X + XO. To understand the involvement of sulfhydryl groups changes in causing depression of Ca(2+)-pump activities, the effects of oxygen free radicals on heart sarcolemmal sulfhydryl groups were also investigated. Heart sarcolemmal sulfhydryl groups were decreased by X + XO in a time-dependent manner. Superoxide dismutase showed a protective effect on sulfhydryl group depression caused by X + XO. N-ethylmaleimide, a sulfhydryl reagent, showed inhibitory effect on Ca(2+)-pump activities both in a time-, and a dose-dependent manner; dithiothreitol and cysteine prevented changes in Ca(2+)-pump activities caused by N-ethylmaleimide. The inhibitory effect of X + XO on Ca(2+)-pump activities were also prevented by the addition of dithiothreitol or cysteine. A significant correlation between changes in sarcolemmal Ca(2+)-stimulated ATPase activity and sarcolemmal sulfhydryl groups was seen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of heart sarcolemmal Ca(2+)-pump activity by oxygen free radicals. 202 66

Effects of oxygen free radicals on Ca2+/Mg2+ ATPase and ATP-independent Ca2(+)-binding activities were examined in rat heart sarcolemma. Membranes were incubated with different oxygen radical generating media such as xanthine + xanthine oxidase, hydrogen peroxide, and hydrogen peroxide + Fe2+. In the presence of xanthine + xanthine oxidase, Ca2+ ATPase activity was stimulated and this effect was prevented by the addition of superoxide dismutase. Hydrogen peroxide also showed a significant increase in Ca2(+)-ATPase activity in a dose-dependent manner and this effect was blocked by catalase. On the other hand, a combination of hydrogen peroxide + Fe2+ decreased Ca2(+)-ATPase activity; this depression was prevented by the addition of D-mannitol. The observed change in Ca2(+)-ATPase activity due to oxygen free radicals was associated with changes in Vmax, whereas Ka remained unaffected. Both xanthine + xanthine oxidase and hydrogen peroxide increased whereas, hydrogen peroxide + Fe2+ inhibited the ATP-independent Ca2(+)-binding activities. It is suggested that oxygen free radicals may influence Ca2+ movements in the cell by altering the Ca2+/Mg2+ ATPase and Ca2(+)-binding activities of the membrane and these effects may be oxygen-radical species specific.
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PMID:Alterations in heart sarcolemmal Ca2(+)-ATPase and Ca2(+)-binding activities due to oxygen free radicals. 215 97

Cat soleus motor nerve terminals, after high frequency conditioning, generate a post-tetanic repetition (PTR) which leads to a post-tetanic (PTP) of the muscle response. This property enables quantitative assessment of enhancement or depression of this nerve terminal excitability in vivo. The present study focuses on ionic mechanisms underlying the PTRs produced in this neuromuscular system either by high frequency stimulation or edrophonium. Ouabain was used as a specific probe for inhibition of Na(+)-K+ ATPase and its known consequences on Na+ and Ca2+ translocation. Ouabain pretreatment doubled the duration over which single stimuli, following either high frequency or edrophonium conditioning produced PTR. Ouabain in the doses used had no effect per se but as a function of dose augmented the frequency dependent responses. This pointed to Na+ loading of nerve terminals via high frequency stimulation plus ouabain inhibition of Na(+)-K+ ATPase. Ouabain potentiation of PTR responses evidently depends on exchange of intra-terminal sodium for external calcium. Thus, calcium entry blockers, Mn2+, and Co2+ suppressed or abolished the potentiations both before and after ouabain. Diphenylhydantoin, a Na+ and Ca2+ blocker, acted similarly. The effects of stimulation frequency, ouabain and the sequence of events leading to PTR in the soleus neuromuscular system appeared in general no different from those derived from the many in vitro microphysiologic studies of this phenomenon. Thus, EPPs were augmented and prolonged. It was concluded that intracellular Ca2+ is critical for regulating the stability of systems in which repetitive firing is both a normal and abnormal function.
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PMID:The interactions of ouabain with post-tetanic and facilitatory drug potentiations at cat soleus neuromuscular junctions in vivo. 216 59


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