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)

The Km value for the dog heart (Na+-K+)-ATPase was 0.31 mM (MgATP), whereas the values for the concentrations of K+ and Na+ varied from 1.2 to 2.7 mM and 12 to 20 mM for half-maximal activation, respectively. The concentrations of ouabain and calcium for 50 percent inhibition of (Na+-K+)-ATPase activity varied from 2.4 to 3.2 muM and 0.5 to 1.2 mM, respectively, the inhibitory effects of these agents were pH dependent. This preparation bound about 50 nmoles of 1-anilino-8-napthaline sulfonate (ANS)/mg of protein and exhibited fluorescence attributable to the ANS-enzyme complex. Cations such as Na+,K+,Ca++, and Mg++ increased ANS-enzyme fluorescence intensity and the number of ANS binding sites but decreased the apparent ANS binding constant. The enzyme activity, ANS binding, and ANS-enzyme fluorescence were decreased by phospholipase A, phospholipase C, and trypsin treatments. Although ouabain inhibited enzyme activity and ANS-enzyme fluorescence markedly, it caused only a slight depression in ANS binding. These results extend support for the allosteric nature of the cardiac (Na+-K+)-ATPase and provide evidence for conformational changes during its activation by Na+ and K+.
 ...
PMID:Characterization of partially purified heart sarcolemmal Na+-K+-stimulated ATPase. 13 Jun 58

1.beta-Bungarotoxin, crotoxin and taipoxin, presynaptic neurotoxins of snake venom origin, have about the same phospholipid-splitting activities as a much less toxic cobra phospholipase A2 in the presence of Ca2+ and deoxycholate. 2. Sr2+ was a much less effective activator of the enzymes than is Ca2+, the activation by Sr2+ being only 3-6% for beta-bungarotoxin and crotoxin and 12% for taipoxin. 3. Sr2+ also inhibited the Ca2+ -activated enzymes by 80% in the cases of beta-bungarotoxin and crotoxin, but only 16% in the case of taipoxin. 4. Mg2" had no significant effect on beta-bungarotoxin or crotoxin, but activated taipoxin in the presence or absence of Ca2". 5. In Sr2+ -Tyrode lacking Ca2+ all three toxins exhibited the same immediate depression followed by facilitation in the rat and mouse diaphragms, but the final blocking activity was only 3-10% with beta-bungarotoxin and crotoxin and was 30% with taipoxin. 6. In Sr2+ -Tyrode, increasing in the rate of nerve stimulation had less accelerating effect on the development of neuromuscular block than in Ca2+ -Tyrode for any of the toxins. 7. Removal of Mg2+ from Sr2+ -Tyrode did not diminish the potency of taipoxin in blocking neuromuscular transmission, suggesting that enzyme activity at the outer surface of the axolemma does not contribute to the neuromuscular blocking action. 8. All of the results indicate that there are close correlations between the presynaptic activities of these toxins and their phospholipid-splitting activities in the cationic environment prevailing in the axoplasm. Apparently the final blocking effect of these toxins is due to phospholipase A action within the nerve terminal.
 ...
PMID:Effects of Sr2+ and Mg2+ on the phospholipase A and the presynaptic neuromuscular blocking actions of beta-bungarotoxin, crotoxin and taipoxin. 19 83

1. The effects of phospholipases A from bee venom and from porcine pancreas and of phospholipases C from Clostridium welchii and Bacillus cereus on active and passive membrane properties of Aplysia neurones have been studied. Consistent alterations in electrical membrane properties were found following intracellular application of three of these enzymes.2. Bee venom phospholipase A produced a rapid decrease of membrane potential and resistance. Voltage clamping revealed a marked depression of peak transient current with little or no effect in the late outward current.3. Mammalian phospholipase A was found ineffective in changing either the resting or active membrane properties.4. Phospholipase C from Bacillus cereus led to a strong hyperpolarization and a fall in membrane resistance. Voltage clamping revealed a marked increase in the late outward current.5. Neurones injected with Clostridium welchii phospholipase C manifested a several-fold rise in resting membrane resistance as well as a tendency to slight hyperpolarization.6. All enzymes were ineffective when externally applied.7. It is tentatively concluded that the internally applied phospholipases affect specific ionic permeabilities both in the resting and active excitable membrane. Various mechanisms by which the differing actions of enzymes of the same type could be explained are discussed.
 ...
PMID:Membrane properties of Aplysia neurones intracellularly injected with phospholipases A and C. 87 92

1. The acidic peptide crotapotin potentiated the toxicity of the basic crotalus phospholipase A in all species tested. The order of sensitivity to the lethal action of the phospholipase was: chick greater than mouse larger than or equal to rabbit greater than rat. After a latency period of a least 20 min the animals died of respiratory paralysis. Rabbits survived for more than 10 h, if they were artificially respired. The animals recovered very slowly from respiratory depression. 2. In rabbits even high doses of the basic crotalus phospholipase A or its complex with crotapotin did not affect the respiratory center nor its reactivity to asphyxia. Conduction of action potentials in the phrenic nerve was not changed. 3. Phospholipase-crotapotin complexes decreased the contractile response of isolated phrenic-hemidiaphragms of rats to direct and indirect stimulation in an irreversible manner. A latency period 20-100 min preceded the paralysis. 4. A similar block of neuromuscular transmission developed in vivo. After i. v. injection of PC-complexes the contractile response of isolated rat phrenic diaphragms to nerve stimulation was considerably lower than to direct stimulation. 5. Crotalus phospholipase A alone as well as its complex with crotapotin reduced the contractions of the isolated chick biventer cervicis muscle but did not cause a contracture, thus indicating that the phospholiphase PC-complexes act not as depolarizing blockers. 6. Blood pressure, heart rate and electrocardiogram were not substantially altered, when phospholipase A or PC-complex were injected slowly i.v. into rabbits or rats. No cardiotoxic effect was observed in the Langendorff preparation of rat hearts perfused with phospholipase A alone (6 x 10(-6) M) or together with crotapotin (10(-5) M). Rapid i.v. injection of the venom produced hypotension. The degree of haemolysis correlated with the enzymatic activity, and was low for the highly toxic PC-complexes.
 ...
PMID:Neurotoxic and myotoxic effects of crotalus phospholipase A and its complex with crotapotin. 94 Jun 5

Using helical strips of the bovine middle cerebral arteries, changes in vascular tension were measured during isometric contractions induced by endothelin. 1) Both Ca(++)-free media and Ca(++)-antagonists depressed the endothelin-induced contractions only by 40% of the control, suggesting the involvement of both Ca(++)-entry from outside the muscle cell and intracellular Ca(++)-release from the sarcoplasmic reticulum. 2) Endothelin-induced contractions were significantly depressed by 1 microgram/ml tetrodotoxin (TTX). Relative size of depression by TTX was practically the same as that observed in Na(+)-free media without TTX. These results indicated a partial involvement of Na(+)-entry through TTX-sensitive Na(+)-channels. 3) Endothelin-induced contractions were effectively depressed by NCDC, an inhibitor of phospholipase C, suggesting the involvement of PI-turnover in the contraction. 4) Protein kinase inhibitors such as H-7 and H-8 effectively depressed endothelin-induced contractions. This result suggested the phosphorylation of a certain protein by protein kinase C as a cause of long lasting contractions. 5) A phospholipase A2 (PL A2) inhibitor, quinacrine, significantly depressed the endothelin-induced contractions, suggesting a possible involvement of PL A2. However, neither the cyclooxygenase inhibitor nor the lipoxygenase inhibitor depressed endothelin-induced contractions.
 ...
PMID:[A pharmacological study on the mechanism of the endothelin-induced contraction of the bovine cerebral artery]. 164 17

Arachidonic acid (AA) is a second messenger liberated via receptor activation of phospholipase A2 or diacylglycerol-lipase. We used whole-cell voltage clamp of acutely isolated hippocampal CA1 pyramidal cells to investigate the hypothesis that AA modulates Ca2+ channel current (ICa) via activation of protein kinase C (PKC) and generation of free radicals. AA depressed ICa in a dose- and time-dependent manner similar to that previously reported for the action of phorbol esters on ICa. A similar depression was seen with a xanthine-based free radical generating system. The specific PKC inhibitor PKCI (19-36), the protein kinase inhibitor H-7, and the superoxide free radical scavenger SOD each blocked ICa depression by 70%-80%. Complete block of the AA response occurred when SOD was used simultaneously with a PKC inhibitor. These data suggest that PKC and free radicals play a role in AA-induced suppression of ICa.
 ...
PMID:Arachidonic acid modulates hippocampal calcium current via protein kinase C and oxygen radicals. 211 31

The direct effects of varying concentrations (5-40 mM) of D,L-carnitine were studied in two populations, subsarcolemmal and interfibrillar, of cardiac mitochondria exposed to inorganic phosphate (Pi). After 5 min preincubation 20 mM Pi significantly depressed oxidative phosphorylation rate and ADP/ATP translocase activity, in both populations. Inclusion of D,L-carnitine during preincubation significantly prevented the Pi-induced depression in oxidative phosphorylation without affecting the ADP/ATP translocate system. The Pi-induced inhibition in mitochondrial oxygen consumption rate was seen with either pyruvate-malate, glutamate-malate or succinate as respiratory substrates and was also observed in uncoupled mitochondria treated with 2,4-dinitrophenol. Mitochondrial swelling and shrinkage studies revealed Pi-induced inner membrane instability, a phenomenon prevented by D,L-carnitine in a dose-dependent manner. The effect of Pi was also observed at a concentration of 5 mM which was also prevented by carnitine. Mepacrine, a phospholipase A2 inhibitor, failed to prevent any of the effects of Pi. The results therefore suggest that Pi can produce a depression in mitochondrial oxidative phosphorylation through a mechanism possibly associated with disturbed inner membrane structure and function but apparently unrelated to phospholipase A2 activation. The salutary actions of carnitine may partly explain its protective effects in the ischemic and reperfused heart, a phenomenon associated with enhanced intracellular Pi accumulation.
 ...
PMID:Reduction of phosphate-induced dysfunction in rat heart mitochondria by carnitine. 225 1

1. Evidence suggests that activation of phospholipase A2 and production of eicosanoids and platelet-activating factor (PAF) are involved in various responses associated with severe tissue damage and shock. It was postulated that the plasma level of the precursor and degradation product of PAF, lyso-platelet-activating factor (lyso-PAF), might be increased in acute severe illness. 2. After plasma extraction, lyso-PAF was acetylated in vitro to PAF, which was measured by bioassay using 5-[14C]hydroxytryptamine-labelled rabbit platelets. Measurements were made in 18 severely ill patients (five with cardiogenic shock; five with severe infection, five after repair of abdominal aortic aneurysm, two with acute pancreatitis; 13 males, five females). Plasma lyso-PAF in these patients was 33 +/- 15 (SD)ng/ml (range 5-111 ng/ml), whereas values in normal males (40-65 years) ranged from 102 to 253 ng/ml (n = 15) and in females from 74 to 174 ng/ml (n = 10). Depression of plasma lyso-PAF did not relate closely to the patient group nor to specific therapy, but repeated measurements in each of 10 patients showed an increase in plasma lyso-PAF (P less than 0.002), associated with clinical improvement. 3. Evidence was obtained indicating that neither the presence of an inhibitor in the assay system nor reconversion of PAF to lyso-PAF in vitro produced the unexpected depression of plasma lyso-PAF. 4. The mechanisms responsible, which may have therapeutic implications, remain to be elucidated.
 ...
PMID:Plasma levels of the lyso-derivative of platelet-activating factor in acute severe systemic illness. 258 28

In order to examine the role of phospholipids in the activation of membrane bound Ca2+/Mg2+ ATPase, the activities of Ca2+ ATPase and Mg2+ ATPase were studied in heart sarcolemma after treatments with phospholipases A, C and D. The Mg2+ ATPase activity was decreased upon treating the sarcolemmal membranes with phospholipases, A, C and D; phospholipase A produced the most dramatic effect. The reduction in Mg2+ ATPase activity by each phospholipase treatment was associated with a decrease in the Vmax value without any changes in the Ka value. The depression of Mg2+ ATPase in the phospholipase treated preparations was not found to be due to release of fatty acids in the medium and was not restored upon reconstitution of these membranes by the addition of synthetic phospholipids such as lecithin, lysolecithin or phosphatidic acid. In contrast to the Mg2+ ATPase, the sarcolemmal Ca2+ ATPase was affected only slightly by phospholipase treatments. The greater sensitivity of Mg2+ ATPase to phospholipase treatments was also apparent when deoxycholate-treated preparations were employed. These results indicate that glycerophospholipids are required for the sarcolemmal Mg2+ ATPase activity to a greater extent in comparison to that for the Ca2+ ATPase activity and the phospholipids associated with Mg2+ ATPase are predominantly exposed at the outer surface of the membrane.
 ...
PMID:Alterations in Ca2+/Mg2+ ATPase activity upon treatment of heart sarcolemma with phospholipases. 296 79

Uranyl ion (UO2+2) antagonized the neuromuscular blocking action and phospholipase A2 activity of neurotoxins which act presynaptically [beta-bungarotoxin (beta-BuTX) and crotoxin] but did not affect the action of alpha-bungarotoxin and tetrodotoxin. On the basis of the kinetic analysis of the UO2+2 and strontium ion (Sr2+) antagonism of muscle paralysis induced by beta-bungarotoxin, it was found that they inhibited both the binding of the toxin and the steps following binding that brought about the neuromuscular blocking action of beta-bungarotoxin. Uranyl ion was about 50 times more potent than Sr2+ in antagonizing beta-bungarotoxin. High Ca2+ (10 mM) abolished but low Ca2+ (0.25-1.25 mM) medium enhanced the antagonizing action of UO2+2 and Sr2+. In low Ca2+ medium, UO2+2 markedly potentiated the amplitude of the twitch, subsequent addition of beta-bungarotoxin produced three phases of effects on the twitches, e.g. an initial depression, followed by the second facilitation and finally a rapid depression of twitches; however, approx. 70 min after beta-bungarotoxin the small twitches reached a steady state which persisted for more than 350 min. Therefore, it is evident that UO2+2 is the most potent antagonist of beta-bungarotoxin so far tested.
 ...
PMID:Antagonistic action of uranyl nitrate on presynaptic neurotoxins from snake venoms. 300 6


1 2 3 4 5 6 7 8 Next >>