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

Evidence is presented in support of the hypothesis that transmitter monoamines can exert their post-synaptic effects by stimulation or inhibition of Na+/K(+)-ATPase in neuronal or glial cell plasma membranes. Stimulation of electrogenic sodium pumping, causing a hyperpolarization with an increase in membrane resistance, could account for the depression of neuronal spontaneous firing and the signal/noise enhancing actions of these amines. Conversely, inhibition of an electrogenic sodium pump in neuronal plasma membranes would lead to depolarization and enhanced excitability.
 ...
PMID:Na+/K(+)-ATPase as an effector of synaptic transmission. 136 11

The effect of perfusate [Ca2+] on the function of cardiac sarcoplasmic reticulum (CSR) was assessed by the oxalate-supported Ca2+ uptake rate of ventricular homogenates of isolated rat hearts maintained in a modified Langendorff preparation. The total Ca2+ pumping activity of the CSR was determined by using 20 microM ruthenium red or 625 microM ryanodine to close the CSR Ca2+ release channel. The homogenate Ca2+ uptake rate in the absence of ruthenium red or ryanodine decreased progressively with increasing perfusate [Ca2+] (25.7 +/- 1.2, 21.4 +/- 1.5, 17.2 +/- 1.1, and 16.3 +/- 1.2 [mean +/- SEM] nmol Ca2+.min-1.mg-1 for hearts perfused for 5 minutes with 0.2, 1.4, 2.8, and 5.6 mM Ca2+, respectively; p = 0.0001; n = 8). This depression was not observed when Ca2+ uptake was assayed in the presence of ryanodine or ruthenium red. Since the Ca2+ uptake in the presence of ryanodine or ruthenium red is determined by the Ca(2+)-ATPase, this result suggests that perfusion with varying [Ca2+] did not affect the Ca(2+)-ATPase. The observed decrease in Ca2+ uptake in the absence of ryanodine or ruthenium red is caused by an increased efflux through the ryanodine-sensitive Ca2+ release channel. When hearts perfused for 5 minutes with 0.2 or 5.6 mM Ca2+ were reperfused for 10 minutes with 1.4 mM Ca2+, homogenate Ca2+ uptake rates were restored to near control levels. These effects of perfusate Ca2+ were not direct effects, because changes in the [Ca2+] of the homogenization medium did not alter the homogenate Ca2+ uptake activity in either the presence or absence of ryanodine. The homogenate Ca2+ uptake rates were unaffected by prior active loading of the CSR with Ca2+. These results suggest a regulatory role of perfusate Ca2+ in increasing the open state of the ryanodine-sensitive Ca2+ release channel that is distinct from the beat-to-beat regulation of Ca2+ release from the CSR by Ca2+ (Ca(2+)-induced Ca2+ release).
 ...
PMID:Effect of perfusate [Ca2+] on cardiac sarcoplasmic reticulum Ca2+ release channel in isolated rat hearts. 138 83

A study is presented on the role of F0 and F1 subunits in oligomycin-sensitive H+ conduction and energy transfer reactions of bovine heart mitochondrial F0F1 H(+)-ATP synthase. Mild treatment with azodicarboxylic acid bis(dimethylamide) (diamide) enhanced oligomycin-sensitive H+ conduction in submitochondrial particles containing F1 attached to F0. This effect was associated with stimulation of the ATPase activity, with no effect on its inhibition by oligomycin, and depression of the 32Pi-ATP exchange. The stimulatory effect of diamide on H+ conduction decreased in particles from which F1 subunits were partially removed by urea. The stimulatory effect exerted by diamide in the submitochondrial particles with F1 attached to F0 was directly correlated with a decrease of the original electrophoretic bands of a subunit of F0 (F0I-PVP protein) and the gamma subunit of F1, with corresponding formation of their cross-linking product. In F0 liposomes, devoid of gamma subunit, diamide failed to stimulate H+ conduction and to cause disappearance of F0I-PVP protein, unless purified gamma subunit was added back. The addition to F0 liposomes of gamma subunit, but not that of alpha and beta subunits, caused per se inhibition of H+ conduction. It is concluded that F0I-PVP and gamma subunits are directly involved in the gate of the F0F1 H(+)-ATP synthase. Data are also presented indicating contribution to the gate of oligomycin-sensitivity conferral protein and of another protein subunit of F0, F6.
 ...
PMID:Role of F0 and F1 subunits in the gating and coupling function of mitochondrial H(+)-ATP synthase. The effect of dithiol reagents. 138 61

Myoglobin is known to protect the mechanical function of the heart from hypoxia by acting as a sarcoplasmic oxygen reservoir and shuttle. We postulated a role for myoglobin in the pathogenesis of congestive heart failure. Several models of congestive heart failure were employed to test the hypothesis, including spontaneous inherited dilated cardiomyopathy in Doberman Pinschers, and heart failure produced by rapid ventricular pacing in dogs, volume overload in chickens and furazolidone toxicity in turkeys. Myocardial myoglobin was decreased by approximately 50% for all models (P less than 0.05). In Doberman Pinschers dogs which are predisposed to the development of dilated cardiomyopathy and have mild subclinical depression of cardiac performance, myocardial myoglobin (1.05 +/- 0.22 mg/g) is approximately 50% decreased compared to healthy mongrel dogs (2.15 +/- 0.52 mg/g), approximately twice as much as dobermans with heart failure (0.47 +/- 0.25 mg/g) but similar to the concentration found in dogs paced to heart failure (1.09 +/- 0.34 mg/g). Myocardium from poultry had remarkably decreased myoglobin compared to mammals (34 +/- 4 micrograms/g) with heart failure produced either by furazolidone or salt toxicity causing a further 50% reduction. In the canine models of heart failure, myocardial myoglobin concentration was demonstrated to be correlated with biochemical and physiological indicators of myocardial performance, namely, mitochondrial and sarcoplasmic reticular ATPase activities, and cardiac output, systemic vascular resistance, pulmonary capillary wedge pressure and mean arterial pressure, respectively. Our data implicates a role for myoglobin deficiency in the pathogenesis of congestive heart failure and in the predisposition of doberman pinschers to dilated cardiomyopathy.
 ...
PMID:Myocardial myoglobin deficiency in various animal models of congestive heart failure. 140 11

Single fibres of different sarcomere length at rest have been isolated from the claw muscle of the yabby (Cherax destructor), a decapod crustacean. Fibres of either long (SL > 6 microns) or short (SL < 4 microns) sarcomere length have been mechanically skinned and were maximally activated by Ca2+ and Sr2+ under various experimental conditions (ionic strength, in the presence of 2,3 butanedione monoxime (BDM)) to determine differences in their contractile properties. Isometric force was measured simultaneously with either myofibrillar MgATPase or fibre stiffness in both fibre types. The ultrastructure of individual long- and short-sarcomere fibres was also determined by electron microscopy. The long-sarcomere fibres developed greater tension (30.48 +/- 1.72 N cm-2) when maximally activated by Ca2+ compared with the short-sarcomere fibres (18.60 +/- 0.80 N cm-2). The difference in the maximum Ca(2+)-activated force can be explained by the difference in the amount of filament overlap between the two fibre types. The maximum Ca(2+)-activated myofibrillar MgATPase rate in the short-sarcomere fibres (1.60 +/- 0.27 mmol ATP l-1s-1) was higher, but not significantly different from the ATPase rate in fibres with long-sarcomeres (1.09 +/- 0.14 mmol ATP l-1s-1). As the concentration of myosin is estimated to be higher only by a factor of 1.22 in the short-sarcomere preparations there is no evidence to suggest that the myofibrillar MgATPase activity is different in the long- and short-sarcomere preparations. The maximum Ca(2+)-activated force (P0) of both short- and long-sarcomere fibres was quite insensitive to BDM compared with vertebrate muscle. Force decreased to 60.2 +/- 5.3% and 76.1 +/- 2.7% in the short- and long-sarcomere fibres respectively in the presence of 100 mmol l-1 BDM. The difference in the force depression between the long- and short-sarcomere fibres is statistically significant (p < 0.05). Fibre stiffness during maximum Ca(2+)-activation expressed as percentage maximum force per nm per half sarcomere was higher by a factor of 3.5 in short-sarcomere fibres than in long-sarcomere fibres suggesting that the compliance of the filaments in the long-sarcomere fibres is considerably higher than in the short-sarcomere fibres. Sr2+ could not activate the contractile apparatus to the same level as that seen by Ca2+ in either fibre type: the maximum Sr(2+)-activated force was (20 +/- 3%) and (63 +/- 3%) of the maximum Ca(2+)-activated force response in short- and long-sarcomere fibres, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Differences in maximal activation properties of skinned short- and long-sarcomere muscle fibres from the claw of the freshwater crustacean Cherax destructor. 149 Oct 74

To examine the signals regulating cardiac growth and molecular structure of subcellular organelles, cardiac hypertrophy was induced in rats by constriction of the abdominal aorta for 12-13 wk or by treatment with a carnitine palmitoyltransferase I inhibitor, etomoxir (12-15 mg/kg body wt) for 12-13 wk. In contrast to pressure overload, etomoxir redistributed the myosin isozyme population from V3 to V1 and increased the sarcoplasmic reticulum (SR) Ca(2+)-stimulated ATPase activity. When rats with pressure-overloaded hearts were treated with etomoxir, the cardiac hypertrophy was increased whereas the shift in myosin isozymes from V1 to V3 was prevented and the depression in SR Ca(2+)-stimulated ATPase activity was reversed. Plasma thyroid hormone and insulin concentrations were not altered but triglyceride concentrations were reduced in etomoxir-treated rats with pressure overload. The data demonstrate a dissociation between cardiac muscle growth and changes in subcellular organelles and indicate that a shift in myocardial substrate utilization may represent an important signal for molecular remodeling of the heart.
 ...
PMID:Modification of subcellular organelles in pressure-overloaded heart by etomoxir, a carnitine palmitoyltransferase I inhibitor. 153 68

Incubation of normal mitochondria at 45 degrees C results in increases of respiration and of total apparent proton conductance (TAPC, respiration/proton motive force) and in an upward shift of the flow-force relationships. Similar effects are observed during operation of the redox proton pumps at different sites of the respiratory chain. These effects are accompanied by an almost equivalent increase of the passive proton conductance (PPC, proton leakage/proton motive force). In mitochondria from 3,3,5-triiodo-L-thyronine (T3)-treated rats there are also increases of respiration and of TAPC and an upward shift of flow-force relationships, more pronounced at the level of the cytochrome oxidase proton pump. However, at variance from the incubation at 45 degrees C, in mitochondria from T3-treated rats there is only a slight increase of PPC. Addition of bovine serum albumin to normal mitochondria incubated at 45 degrees C results in a marked depression of TAPC in the nonlinear range of the flow-force relationships. An equivalent effect is not observed in mitochondria from T3-treated rats. The experimental results have been compared with computer simulations obtained on the basis of a chemiosmotic model of energy transduction. The increase of TAPC following incubation at high temperature is apparently due to changes of the proton conductance mainly at the level of PPC, while the increase of TAPC following T3 administration is rather due to changes presumably at the level of the redox or ATPase proton pumps.
 ...
PMID:Mechanism of loss of thermodynamic control in mitochondria due to hyperthyroidism and temperature. 163 81

The effect of inhibitors of proton pumps, of uncouplers and of permeant ions on the relationship between input force, delta mu H+, and output flows of the ATPase, redox and transhydrogenase H(+)-pumps in submitochondrial particles was investigated. It is concluded that: (1) The decrease of output flow of the transhydrogenase proton pump, defined as the rate of reduction of NADP+ by NADH, is linearily correlated with the decrease of input force, delta mu H+, in an extended range of delta mu H+, independently of whether the H(+)-generating pump is the ATPase or a redox pump, or whether delta mu H+ is depressed by inhibitors of the H(+)-generating pump such as oligomycin or malonate, or by uncouplers. (2) The output flows of the ATPase and of the site I redox H(+)-pumps exhibit a steep dependence on delta mu H+. The flow-force relationships differ depending on whether the depression of delta mu H+ is induced by inhibitors of the H(+)-generating pump, by uncouplers or by lipophilic anions. (3) With the ATPase as H(+)-consuming pump, at equivalent delta mu H+ values, the output flow is more markedly inhibited by malonate than by uncouplers; the latter, however, are more inhibitory than lipophilic anions such as ClO4-. With redox site I as proton-consuming pump, at equivalent delta mu H+ values, the output flow is more markedly inhibited by oligomycin than by uncouplers; again, uncouplers are more inhibitory than ClO4-. (4) The results provide further support for a delocalized interaction of transhydrogenase with other H(+)-pumps.
 ...
PMID:Flow-force relationships during energy transfer between mitochondrial proton pumps. 164 34

Denervated fast-twitch rabbit muscles were progressively losing their fresh weight and the yield of sarcotubular protein was increasing. The activity of Ca(2+)-ATPase was affected but very slightly, the basal Mg(2+)-ATPase and the Mg(2+)-ATPase/Ca(2+)-ATPase ratio however increased together with a simultaneous depression of the membrane-bound acetylcholinesterase activity. We did not observe any differences in density properties of sarcotubular fractions between control and denervated muscle. However, a relative enrichment in SM and H fraction could be seen after denervation with small changes in the content of the Ca(2+)-pump protein, increased levels of calsequestrin and cholesterol, mostly in the heavy and the SM fraction. After denervation the binding sites for 3H-PN-200-110 did not show any changes in receptor affinity, but the number of putative Ca(2+)-channels increased twice along with a depression of 3H-ouabain binding sites. We suggest that the denervation of fast-twitch muscle leads to the hypertrophy of the junctional sarcoplasmic reticulum and the T-system. Changes in the cholesterol content, in the number of putative Ca(2+)-channels and in Na+, K(+)-ATPase can affect the muscle contraction.
 ...
PMID:Effects of denervation on the contents of cholesterol and membrane systems involved in muscle contraction in rabbit fast-twitch sarcotubular system. 165 Jul 29

During the development of large bowel cancer alterations in colonic epithelial ion transport have been observed some of which result in altered intracellular ionic composition. In many tumors intracellular sodium and potassium become elevated and depressed, respectively. This observation suggests that mechanisms governing intracellular homeostasis for sodium and potassium are no longer tightly regulated. Changes in cell membrane permeability, sodium, potassium-ATPase K(+)-ATPase) pump activity, or both may be responsible for these alterations. It is not known when during initiation and development of cancer such changes may occur. To assess whether there are changes in the Na+, K(+)-ATPase pump early during the induction of large bowel cancer and prior to any notable histological changes, we measured the kinetics of the Na+, K(+)-pump in distal colonic mucosa of CF1 mice one week following only four weekly injections of the carcinogen 1,2-dimethyhydrazine (DMH). The kinetics of the pump were found to be best described by a model of highly cooperative binding. The VMAX of the pump in premalignant mucosa was lower for both sodium and potassium substrate activation (55-65% of control) with little change in other kinetic parameters. Depression of VMAX could not be attributed to an increased barium blockable potassium conductance of the basolateral membrane. Na+,K(+)-ATPase activity was also decreased by 50% in the distal colon of DMH treated mice, but was not affected in the less cancer susceptible proximal colon. These data demonstrate that alterations occur in the Na+,K(+)-pump in premalignant mucosa months before gross tumors develop, and these changes may partially explain the altered levels of Na+ and K+ in the cytoplasm of pre-malignant and malignant colonocytes.
 ...
PMID:Inhibition of the Na+,K(+)-ATPase pump during induction of experimental colon cancer. 166 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>