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)

Transient ischemia does not induce myocardial necrosis but may be associated with prolonged contractile dysfunction ("stunned" myocardium). It has been suggested that alteration of the excitation-contraction coupling system (sarcoplasmic reticulum) could be responsible for this phenomenon. We tested this hypothesis by characterizing sarcoplasmic reticulum (SR) function in an isolated rat heart model of "stunned" myocardium (hearts reperfused after 10 min of normothermic global ischemia). At the end of the ischemic period oxalate-supported Ca-uptake was depressed either in the whole homogenate or in isolated SR (to 47% and 22% of control values, respectively). During reperfusion Ca-uptake of the whole heart homogenate recovered almost completely whereas slight but significant depression persisted in isolated SR (48 +/- 2 vs 67 +/- 4 nmol/min x mg, P less than 0.01). In the presence of ruthenium red or ryanodine, two inhibitors of SR Ca-release channels, Ca-uptake was stimulated. Both in the whole heart homogenate and in isolated SR, such stimulation was remarkably smaller after reperfusion than in control conditions (P less than 0.001) suggesting reduced conductivity state of the SR Ca-release channels. Ca-stimulated, magnesium-dependent ATPase activity was remarkably reduced during ischemia and postischemic reperfusion induced only incomplete recovery (93 +/- 18 vs 169 +/- 14 nmol ATP/min x mg protein, P less than 0.05). We conclude that complex modifications of SR function occur in the "stunned" myocardium and could contribute to the contractile impairment found in this condition.
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PMID:Sarcoplasmic reticulum function in the "stunned" myocardium. 247 59

1. The effects of a six week period of streptozotocin-induced diabetes on tissue catecholamines and on in vivo noradrenaline turnover were assessed in rats. 2. Noradrenaline concentrations measured in heart ventricle, terminal ileum, vas deferens, spleen and adrenal tissue from the diabetic rats were all found to be elevated compared to those found in control rat tissues. The adrenaline contents of the adrenal glands were also raised in these animals. 3. Noradrenaline turnover in heart ventricle, terminal ileum and vas deferens was estimated from the decline in tissue content of the amine following inhibition of its synthesis with alpha-methyl-p-tyrosine. Turnover was found to be increased in all three tissues. 4. The involvement of the polyol pathway in the above changes was investigated by examining the effects of continuous treatment with an aldose reductase inhibitor, Statil (ICI 128436) or dietary myo-inositol supplementation. Either treatment was found to prevent or reduce the increases in tissue noradrenaline and in its turnover. Myo-inositol treatment also partially prevented the rise in adrenal adrenaline. 5. It is concluded that the elevation of tissue catecholamines and of noradrenaline turnover by diabetes was related to myo-inositol depletion secondary to excessive sorbitol synthesis. Possible mechanisms for the observed increase in noradrenaline turnover could involve Na+, K+-ATPase depression.
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PMID:Tissue noradrenaline and the polyol pathway in experimentally diabetic rats. 250 23

Three and 11 wk after coronary artery ligation in rats, the right and left ventricular free wall, septum, and papillary muscles from infarcted and sham-operated hearts were analyzed to determine whether regional variability existed in cardiac actomyosin adenosine triphosphate (ATPase) activity and myosin isoenzymes. Infarction produced a 74% greater right ventricular mass and 19% greater septal mass compared with sham-operated hearts at 3 wk. There was no additional increase in cardiac mass associated with infarction from 3 to 11 wk above that expected for normal growth. Actomyosin ATPase activity and the percent V1 myosin heavy-chain isoenzyme decreased significantly in all regions of the infarcted heart by 3 wk. In addition, the left ventricular and papillary muscle of infarcted hearts exhibited a decrease in percent V1 myosin of 18 and 35%, respectively, compared with the right ventricular free wall and septum. These differences persisted at 11 wk, although no further depression of actomyosin ATPase activity or shift in myosin isoenzyme distribution were observed over the 8-wk period. These results demonstrate that myocardial infarction induces a shift in the myosin isoenzyme distribution and depression in actomyosin ATPase activity of surviving cardiac tissue. Regional variability in myosin isoenzymes is evident by 3 wk, but additional adaptation in cardiac mass and myosin biochemistry do not occur beyond this time.
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PMID:Regional variation in rat cardiac myosin isoenzymes and ATPase activity after infarction. 252 83

Sarcoplasmic reticulum (SR) Ca2+ uptake and Ca2+-Mg2+-ATPase activity were examined in muscle homogenates and the purified SR fraction of the superficial and deep fibers of the gastrocnemius and vastus muscles of the rat after treadmill runs of 20 or 45 min or to exhaustion (avg time to exhaustion 140 min). Vesicle intactness and cross-contamination of isolated SR were estimated using a calcium ionophore and mitochondrial and sarcolemmal marker enzymes, respectively. Present findings confirm previously reported fiber-type specific depression in the initial rate and maximum capacity of Ca2+ uptake and altered ATPase activity after exercise. Depression of the Ca2+-stimulated ATPase activity of the enzyme was evident after greater than or equal to 20 min of exercise in SR isolated from the deep fibers of these muscles. The lowered ATPase activity was followed by a depression in the initial rate of Ca2+ uptake in both muscle homogenates and isolated SR fractions after greater than or equal to 45 min of exercise. Maximum Ca2+ uptake capacity was lower in isolated SR only after exhaustive exercise. Ca2+ uptake and Ca2+-sensitive ATPase activity were not affected at any duration of exercise in SR isolated from superficial fibers of these muscles; however, the Mg2+-dependent ATPase activity was increased after 45 min and exhaustive exercise bouts. The alterations in SR function could not be attributed to disrupted vesicles or differential contamination in the SR from exercise groups and were reinforced by similar changes in Ca2+ uptake in crude muscle homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of exercise of varying duration on sarcoplasmic reticulum function. 252 76

Ethanol, in vitro, decreases muscle fiber twitch tension by a mechanism unrelated to the electrical events of the motor end-plate or muscle surface membranes, an effect which may be attributable to a primary ethanol effect on the calcium release process of the sarcoplasmic reticulum. In this study, ethanol was found to progressively decrease a form of calcium release from isolated sarcoplasmic reticulum vesicles seen after calcium loading in high-phosphate media (spontaneous calcium release). Elevated extravesicular free calcium concentrations are known to inhibit spontaneous calcium release, and the ability of sarcoplasmic reticulum to achieve and maintain submicromolar extravesicular free calcium concentrations in the presence of ethanol was therefore determined. Ethanol had no effect on the low extravesicular free calcium concentrations achieved by isolated sarcoplasmic reticulum, and had no effect on residual ATPase activity remaining after cessation of calcium pumping. This latter result suggests that efflux of vesicular calcium and persistent calcium reaccumulation do not occur in the presence of ethanol. These results suggest that ethanol-induced depression of spontaneous calcium release is not attributable to ethanol effects on sarcoplasmic reticulum membrane calcium leakage or on sarcoplasmic reticulum calcium pumping. Ethanol inhibition of spontaneous calcium release from isolated sarcopasmic reticulum may reflect an effect of ethanol on the calcium release process in intact muscle fibers responsible for ethanol-induced decreases in muscle fiber twitch tension.
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PMID:Ethanol inhibition of spontaneous calcium release from isolated sarcoplasmic reticulum. 253 74

Neurotransmitter receptor binding and Na+, K+-ATPase activity were examined in the brains of six rats exposed to 7 days of microgravity during the flight of Spacelab 3. The same variables were examined in a group of six ground control rats. 5-HT1 receptor number in the hippocampus was significantly elevated by exposure to the microgravity environment, and cortical sodium-potassium pump activity was significantly depressed. A marginal depression in dopamine D-2 binding in the striatum was noted. Dopamine and 5-HT binding in a wide variety of other central regions, in addition to GABAA, muscarinic acetylcholine, adenosine A1, and opiate receptor binding, and adrenoceptor binding, was unaffected by microgravity exposure.
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PMID:Effects of microgravity on brain neurotransmitter receptors. 254 43

Current theories of affective disorders do not account for many of the biological markers replicated in patient studies. We link many biological findings in a reasonable physiological relationship, compatible with mechanisms of action of pharmacological and electroshock therapies for depression. We propose that excessive phospholipase-A2 (PLA2) activity disrupts membrane fluidity, composition, and therefore, the activity, of membrane-dependent proteins. Similar disruptions in these proteins are documented in depressed patients and can be accounted for by excessive PLA2 activity. This paradigm accounts for disturbances in the activity of Na-K-ATPase, beta2- and alpha2-adrenergic receptors, MAO, norepinephrine and serotonin uptake, and imipramine binding. Disturbances in other membrane-dependent proteins, tyrosine and tryptophan hydroxylase, can explain the biogenic amine hypothesis. Inhibition of glucocorticoid receptor and TRH receptor binding to their respective ligands by PLA2 may explain patient nonsuppression in the Dexamethasone Suppression Test and poor response in the TRH stimulation test. Physiological regulators of PLA2 activity; calcium, cortisol, estrogen, progesterone, and PGE2 are documented abnormalities in some patients with affective disorders and consistent with excessive PLA2 activity. Thus, postpartum depression and premenstrual tension syndrome may be described in the paradigm. The mechanisms of action of tricyclic antidepressants, lithium, electroconvulsive shock, and some novel antimanic agents can be described in terms of alterations of PLA2 activity. Interestingly, ethanol perturbs membrane fluidity and membrane-bound enzymes in a manner similar to excessive PLA2 activity. A hereditary factor predisposing patients to affective disorders may be a gene defect at either PLA2 or in its regulation.
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PMID:Are disturbances in lipid-protein interactions by phospholipase-A2 a predisposing factor in affective illness? 256 35

The ototoxicity of an otic drop preparation containing 2% acetic acid and 3% propylene glycol (VoSol, Denver Chemical Co., Humacao, PR) was investigated according to measurements of endocochlear potential (EP) and inner ear fluid pH. The application of this preparation to the round window membrane for 30 minutes caused a depression in EP from 80.5 +/- 2.5 mV (mean +/- SD; n = 6) to 11.7 +/- 7.7 mV, and lowered inner ear fluid pH from 7.55 +/- 0.09 to 5.06 +/- 0.19 (n = 6) in perilymph and from 7.52 +/- 0.07 to 5.88 +/- 0.63 (n = 6) in endolymph. Two percent acetic acid produced similar changes after 30 minutes: EP was reduced from 83.0 +/- 2.2 mV to 34.0 +/- 2.9 mV and endolymphatic pH from 7.49 +/- 0.04 to 6.83 +/- 0.21 (n = 4). However, the application of artificial perilymph of pH 4 titrated with HCl induced no significant changes in either EP or endolymphatic pH. We suggest that the mechanisms of ototoxicity in the otic drop preparation are Na+ and K+-ATPase inhibition, and that such inhibition is due to the intracellular acidification of strial cells resulting from the penetration of acetic acid across the cell membrane, and to the direct and synergistic actions of propylene glycol.
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PMID:The preparation of acetic acid for use in otic drops and its effect on endocochlear potential and pH in inner ear fluid. 259 25

1. Firing thresholds and conduction latencies of single myelinated axons in frog sciatic nerves were monitored during impulse activity in vitro. Resting threshold and the activity dependence of threshold were studied as a function of the concentration of two inhalational anaesthetic agents, halothane and enflurane. 2. At concentrations comparable to those obtained during general anaesthesia both agents produced biphasic effects on the resting threshold. A step increase in the partial pressure of anaesthetic was followed first by a transient lowering of threshold, then by a slow rise to a steady-state level above the original baseline. Step decreases in anaesthetic were followed by transient rises before threshold dropped. Transients lasted 20-30 min. During these threshold transients, the average latency of impulse conduction changed monotonically. The prolongation of latency following an increase in anaesthetic was progressive, reaching steady state concurrently with threshold (20 min to greater than 1 h). 3. The anaesthetics reduced the long-lasting increased threshold ('depression') which normally follows repetitive impulse activity in axon membrane. 4. These actions of halothane at concentrations of 0.25-2.7% (0.14-1.54 mM) and enflurane at concentrations of 0.62-3.08% (0.35-1.73 mM) on resting threshold and on the activity-dependent increase in threshold increased monotonically with anaesthetic concentration. 5. The effects on excitability at steady state are consistent with block of voltage-dependent Na+ and K+ channels by these inhalational agents. Reduced depression may occur because the anaesthetics reduce the net ion transfer per impulse, slowing the substrate-driven Na+-K+-ATPase and thereby reducing electrogenic hyper-polarization. 6. The finding that general anaesthetics inhibit depression at clinically relevant concentrations supports the possibility that general anaesthesia is produced by inhibition of processes that modulate excitability of nerve membrane. We suggest that general anaesthetics produce unconsciousness and amnesia because they disrupt activity-dependent processes, which may thus remove temporal 'context' essential for interpreting nerve impulse patterns.
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PMID:Effects of halothane and enflurane on firing threshold of frog myelinated axons. 261 30

Plasma and urine levels of an endogenous digitalis-like compound (EDLC) are increased in low renin Na+-dependent experimental hypertension, in some normotensive offspring of hypertensive patients and in some essential hypertensive patients. Urine-drived EDLC was purified from 550 L of urine from essential hypertensive patients (n = 8) and from normotensive subjects with a family history of hypertension (n = 27), using flash chromatography on C18 reversed-phase, anion exchange chromatography and various reversed-phase high performance liquid chromatographies. The mechanism of Na+-K+ ATPase inhibition and the related effects of semipurified urine-derived EDLC were studied and compared with those of ouabain. Its action was similar to that of ouabain in 8 out of 10 of the tests applied. The main effects of such a compound were the depression of Na+-K+ pump activity of human erythrocytes, the inhibition of 5-hydroxytryptamine reuptake by human platelets, and the induction of natriuresis in urethanized rats. Therefore, EDLC may be considered as one of the natriuretic hormones whose mechanism of action closely resembles that of ouabain.
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PMID:An endogenous digitalis-like compound extracted from human urine: biochemical and chemical studies. 282 38


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