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)

1. The velocity of shortening at zero load was studied during fused tetanic contractions and single twitches in isolated skeletal muscle fibres of Rana temporaria. 2. The technique used for determination of the speed of unloaded shortening consisted of a series of quick releases of different amplitudes applied at a given instant during activity. The time, delta t, needed for the fibre to take up the slack was plotted against the amplitude of release, delta L. The slope of the straight line relating delta t-delta L provided a measure of the velocity of shortening at zero load, V0. 3. V0 was compared with force-velocity data obtained at finite loads (load-clamp recordings). The predicted velocity of shortening at zero load, derived by hyperbolic extrapolation from velocities at low and intermediate loads, was not significantly different from V0. 4. The temperature dependence of isometric force and of shortening velocity was investigated between 2 and 12 degrees C in the same fibres. Q10 was 2.67 +/- 0.07 (S.E. of mean, n = 6) for V0 and 1.24 +/- 0.01 for tetanic force. 5. The velocity of unloaded shortening was determined at different sarcomere lengths in the range 1.4--3.1 microns. V0 was constant between 1.65 microns and approximately 2.7 microns. It decreased below 1.65 microns and increased above 2.7 microns. 6. The decrease in velocity at short sarcomere lengths probably reflects an increase of the passive resistance to shortening. The increase in velocity at long sarcomere lengths can be accounted for by the passive compressive force that is produced by the parallel elastic elements of the prestretched fibre. 7. V0 was determined at the peak of the twitch and during the plateau of the fused tetanus in the same fibre. Whereas the peak twitch force varied between 38 and 85% of the tetanic tension in the different fibres (mean: 71 +/- 5%, n = 8), V0 during the twitch was 99 +/- 2% of the value recorded during the tetanus. Depression of the isometric twitch amplitude to 10% of the control value by dantrolene did not cause any significant reduction of V0.
 ...
PMID:The velocity of unloaded shortening and its relation to sarcomere length and isometric force in vertebrate muscle fibres. 31 10

1. Acetylcholine (ACh), 7.5 x 10(-5) M, and carbachol, 5 x 10(-6) M (CCh) depressed the frequency of miniature endplate potentials (m.e.p.ps) in the frog (Rana temporaria) sartorius neuromuscular junction with active acetylcholinesterase to about 50-55% of the controls. 2. A similar depression was produced by the nicotinic agonists, nicotine, suberyldicholine and tetramethylammonium. 3. The muscarinic agonists, oxotremorine, methylfurmethide and methacholine were without effect on m.e.p.p. frequency. The muscarinic antagonist, atropine and the nicotinic antagonist, (+)-tubocurarine, had no effect on the depression of m.e.p.p. frequency evoked by CCh. 4. The ganglionic blockers, benzhexonium and IEM-1119, were also without effect on the CCh-evoked depression of m.e.p.p. frequency. 5. Pretreatment of muscles with anticholinesterases did not prevent the CCh-induced drop in m.e.p.p. frequency. 6. The effect of CCh was proportionally the same as in the controls in preparations where the m.e.p.p. frequency was changed by elevation of K+ and in the presence of theophylline, noradrenaline, dibutyryl adenosine 3':5'-cyclic monophosphate (db cyclic AMP) and db cyclic GMP. 7. An inhibitor of Na+,K(+)-ATPase, ouabain, 5 x 10(-5) mol l-1, prevented or reversed the depression of m.e.p.p. frequency by CCh. However, the depression was present in a nominally K(+)-free medium. Insulin and adrenaline, which are considered to be Na+,K(+)-ATPase activators, were without effect on depression of m.e.p.p. frequency. 8. The depression of m.e.p.p. frequency by 5 x 10(-6) M CCh was the same at temperatures between 5 and 30 degrees C with a Q10 near to 1.0. When threshold amounts of CCh were used (6 x 10-7 and 3 x 10-7 M), the depression was less at higher temperatures.9. The receptive structures responsible for the CCh (or ACh)-evoked depression of m.e.p.p. frequency differ pharmacologically from muscarinic, nicotinic ganglionic and neuromuscular junction ACh-receptors as well as from the synaptic cholinesterase, in contrast to previous reports (Duncan & Publicover, 1979).The low temperature-dependence points to the possibility that physical rather than biochemical processes are limiting in this presynaptic effect of cholinomimetics.
 ...
PMID:Depression of miniature endplate potential frequency by acetylcholine and its analogues in frog. 166 83

De novo phospholipid biosynthesis was assayed in isolated hepatocytes of rainbow trout (Oncorhynchus mykiss) both fully acclimated to 5 or 20 degrees C and undergoing acclimation from one temperature extreme to the other. Incorporation of [14C]choline, [3H]ethanolamine, and [3H]serine into phosphatidyl-choline (PC), phosphatidylethanolamine (PE), or both, was followed to assess metabolic capacity. PE biosynthesis rates exceeded those for PC four- to fivefold. Methylation of PE accounted for 10 (20 degrees C)-17% (5 degrees C) of the synthetic capacity for PC, whereas 6 (20 degrees C-acclimated)-27% (5 degrees C-acclimated) of PE synthesis was derived from phosphatidylserine (PS) decarboxylation. Several factors may contribute to the altered proportions of PE and PC or unsaturated molecular species of phospholipids characteristic of thermally acclimated animals. 1) Activities of choline and ethanolamine phosphotransferase pathways were significantly higher, and decarboxylation activity lower, in 20 degrees C than in 5 degrees C-acclimated trout, resulting in maintained PE synthesis despite a general depression of lipid biosynthesis at cold temperatures. 2) PC biosynthesis depended more on temperature (Q10 = 2.6-3.0) than that of PE (Q10 = 1.8-2.2), causing the ratio of PC/PE synthesis to be positively correlated with temperature. 3) Contribution of methyltransferase pathway to the synthesis of PC was higher at 5 than 20 degrees C. 4) The percentage of ethanolamine incorporation recovered in PC increased threefold in the early stages of warm acclimation. However, not all adjustments in biosynthetic capacity (most notably a 10-fold stimulation of PC synthesis 2 days after transfer of warm-acclimated trout to 5 degrees C) influence membrane lipid composition, implicating other processes in the regulation of this parameter.
 ...
PMID:Adaptation to temperature: phospholipid synthesis in hepatocytes of rainbow trout. 216 24

The effect of temperature on the force-sarcomere velocity relation (20 degrees, 25 degrees, and 30 degrees C) and maximum velocity of sarcomere shortening (Vo; range 15 degrees-35 degrees C) was studied in trabeculae from rat heart. Sarcomere length and Vo were measured by laser diffraction techniques. Sarcomere length and sarcomere velocity, determined from each of the first-order diffraction lines, differed by less than 4%. Slack sarcomere length in the trabeculae appeared to be 1.9 microns. Isovelocity release techniques were used to obtain sarcomere velocity and Vo directly. Sarcomere velocity was measured at SL = 1.9-2.0 microns for elimination of contributions of parallel elastic force and restoring force to the external load of the sarcomeres. Peak twitch force development (Fo) was maximal (Fo-max) at 25 degrees C at [Ca2+]o = 1.5 mM. Lowering of the temperature below 25 degrees C led to development of spontaneous sarcomere activity and depression of Fo; both responses could be prevented by the addition of 0.5 mM procaine. Increase of temperature above 25 degrees C reduced twitch duration and Fo. Hill's rectangular hyperbola fitted the force-velocity data if the load during shortening was less than 70% of Fo. Vo appeared to be independent of the level of activation at all temperatures when Fo was maintained above 90% of Fo-max, either by an increase of [Ca2+]o (to 3.0 mM) or by paired pulse stimulation. Vo increased with increasing temperature; the parameter a, calculated from force-velocity relations measured at 20 degrees, 25 degrees, and 30 degrees C, decreased with increasing temperature. The Arrhenius plot of Vo was studied in detail over a wider temperature range (15 degrees-35 degrees C) and in smaller temperature increments. The relation was linear between 18 degrees and 33 degrees C; the observed Q10, defined as the ratio of Vo measured at temperature (T) over Vo at T-10 degrees C, was 4.6 A Q10 of 4.6 for Vo is consistent with the reported temperature dependence of rat cardiac actin-activated myosin ATPase, which suggests that the same reaction step may limit the activity of the enzyme in vitro and during shortening of the cardiac sarcomeres at zero external load.
 ...
PMID:Force and velocity of sarcomere shortening in trabeculae from rat heart. Effects of temperature. 233 24

ICa was recorded in guinea pig ventricular myocytes using the whole-cell voltage-clamp technique. The shape of the I-V relation was unaffected by temperature (21-37 degrees C) but there were large changes in ICa amplitude and time course. Steady-state responses indicated Q10's of 2.96 +/- 0.14 (amplitude), 2.52 +/- 0.13 (time to peak), and 2.82 +/- 0.28 (T1/2 inactivation) (mean +/- SD, n = 6). Quick changes in temperature (T1/2 less than 30 s) induced pronounced deviations from the steady-state Q10 relations (early depression, compensatory overshoot). Thus, cardiac ICa differs from other currents in having a high amplitude-Q10 and an oscillatory response to rapid temperature changes.
 ...
PMID:Temperature-induced transitory and steady-state changes in the calcium current of guinea pig ventricular myocytes. 241 20

Intracellular potentials were recorded from inner hair cells in the guinea pig cochlea. Transient asphyxia was induced by interrupting respiration for brief periods. Asphyxia caused a hyperpolarization of the resting membrane potential (resting Em). The hyperpolarization averaged 2.9 mV for 30 s asphyxias and 5.7 mV for 45 s asphyxias. The membrane potential recovered quickly after normal ventilation was resumed. Asphyxia also induced a rapid and profound decrease of the d.c. receptor potential in response to moderate intensity tone bursts at the characteristic frequency of the inner hair cell. At maximal depression, the receptor potential was reduced about 60% for a 30 s asphyxia and 100% for a 45 s asphyxia. The receptor potential recovered slowly after normal ventilation was resumed. A similar percent reduction and time course of recovery were observed for the a.c. receptor potential. In recordings from the same animals, the round window compound action potential (CAP) was as severely depressed by asphyxia as the hair cell receptor potentials. The time course of recovery for the CAP was similar to the slow recovery of the d.c. receptor potential. In contrast, the round window cochlear microphonics (CM) and the endolymphatic potential (EP) were affected less by asphyxia and recovered quickly after ventilation was resumed. Frequency tuning curves (FTCs) for the d.c. receptor potential were measured during the period of maximal receptor potential depression. These FTCs showed decreased tip sensitivity and a decrease in sharpness of tuning, as measured by the Q10. These changes were fully reversible. Low frequency (tail) segments of the FTCs were much less affected by asphyxia. The inner hair cell FTC changes during asphyxia were compared with neural FTC changes reported by other investigators. The similarities lead us to the conclusion that the inner hair cell and the auditory neural response to sound are equally sensitive to asphyxia.
 ...
PMID:Cochlear inner hair cells: effects of transient asphyxia on intracellular potentials. 683 58

Immunopotentiators may mitigate the depression of immunological function caused by the cancer itself or by chemotherapeutics. However, it has been found that these immunopotentiators reduce the metabolic activity of the host against drugs, including "masked" chemotherapeutics, which might be activated by metabolization in the body. Reported here is the result of serial experiments carried out on the activation of cyclophosphamide (CPM) in tumor-bearing animals, pretreated with phenobarbital, a drug-metabolizing enzyme inducer, and coenzyme Q10, a physiological activator of the electron transfer system in mitochondrias, in combination with immunopotentiators. Female Donryu rats (120 g body weight) implanted with Yoshida Sarcoma cells (YS) (2.5 X 10(6) i.p.) were treated with CPM (160 mg/kg X 1 i.p.), 84 hrs after implantation; the levels of the normustard-like substances (active metabolites of CPM) were serially measured. Some of the animals were also treated with PSK (125 mg/kg X 5 i.p.), a proteinpolysaccharide immunopotentiator obtained from mycelia of the Coriolus vesicolor, or with OK-432 (10 KE/kg X 5 i.m.), a streptococcal immunopotentiator. The results obtained were as follows: The blood levels of the normustard-like substances were lowered, i.e. the CPM activation was depressed in the YS-bearing rats and the depression was markedly intensified by PSK or OK-432 administration. Phenobarbital (40 mg/kg X 3 i.p.) or coenzyme Q10 (5 mg/rat X 5 i.p.) administration could mitigate the depression of the blood levels caused by the immunopotentiators, and the combination of phenobarbital with coenzyme Q10 could recover the blood levels up to those of the YS-bearing control rats, or even higher. YS-implanted (i.p.) rats treated with CPM+ immunopotentiators+coenzyme Q10 survived longer than those treated with CPM+immunopotentiators. These findings suggest the usefulness of coenzyme Q10 for the enhancement of cancer immunochemotherapy using masked compounds combined with immunopotentiators; all the more so, because coenzyme Q10 has also an immuno-stimulating effect, moreover, it presents almost no side effects in clinical application.
 ...
PMID:[Coenzyme Q10 in cancer chemotherapy--experimental studies on augmentation of the effects of masked compounds, especially in the combined chemotherapy with immunopotentiators]. 688 95

Shortening during activity of frog single muscle fibres caused a graded depression of the contractile force that persisted for 800-900 ms during a partially fused or completely fused tetanus. The depression of force was not associated with a change of the shortening velocity at zero load. Passive shortening performed just before stimulation had no effect on the subsequent course of contraction. The decrease in isometric force produced by shortening was not significantly affected by a stretch applied immediately before or after the shortening was not significantly affected by a stretch applied immediately before or after the shortening phase. For a given amount of shortening the depressant effect during a fused tetanus was 8-28% of that produced during a twitch. The effect was substantially reduced, both during twitch and tetanus, in the presence of 0.5 mM caffeine. The length dependence of the movement effect was studied between 1.7 and 2.9 micrometer sarcomere spacing. Maximum depression of force (in per cent of the control at each length) was obtained at 2.1-2.2 micrometer sarcomere length, the effect being steadily reduced at shorter and more extended lengths. The Q10 of the depressant effect was 0.95 +/- 0.16 (S.D.). The features of the movement effect are consistent with a true deactivation of the contractile system as would occur if shortening reduced the binding of activator calcium to the regulatory proteins of the myofilaments.
 ...
PMID:Depression of mechanical performance by active shortening during twitch and tetanus of vertebrate muscle fibres. 696 30

Spreading depression (SD) occurs in the cerebellum of an elasmobranch fish, the skate (Raja erinacea, Raja ocellata). The elasmobranch cerebellum, because of its unique separation of granular form molecular layer, provides an excellent opportunity to study the characteristics of SD in two distinct neuronal populations. Both the DC potential shifts and changes in neuronal activity effected by SD were analyzed. The SD DC potential shifts in both layers closely resembled those in mammalian cerebral cortices. Consisting of a predominantly negative extracellular potential shift, they were typically 1--10 min in duration and reached 5--40 mV peak amplitudes. The largest negative shifts were found in the granular layer, without any consistent positive phases in the white matter, molecular, or granular layers. The SD propagated radially from surface electrical stimulation at 0.78 mm/min (+/- 0.16, n = 8) in the molecular layer and 0.43 mm/min (+/- 0.17, n = 8) in the granular layer at 15 degrees C. At 18 degrees C, the molecular layer propagatory velocity was 1.1 mm/min (+/- 0.12, n = 20) while, at 10 degrees C, it was 0.52 mm/min (+/- 0.21, n = 20), suggesting a temperature-dependent Q10 factor of 2. A profound depression of both spontaneous and evoked neuronal activity accompanied the DC potential shift. Activation of Purkinje cells antidromically, white matter, and granular layer neurons was typically abolished by the peak of the negative DC shift. However, a significant increase in granular layer excitability often followed the neuronal depression, remaining so far up to an hour. Repeated waves of SD sometimes occurred in the absence of neuronal recovery. A similar post-SD excitability increase was not seen in molecular layer neurons. Intracellular recordings from Purkinje cells revealed a spontaneous burst of action potentials at the onset of SD, closely followed by a depolarization of membrane potential from an average of -64 mV (+/- 12 mV, n = 3) to -11 mV (+/- 5 mV, n = 3).
 ...
PMID:Spreading depression in elasmobranch cerebellum. 740 17

1. The properties of evoked excitatory postsynaptic currents (EPSCs) and spontaneous miniature excitatory postsynaptic currents (mEPSCs) have been studied in neurons of the nucleus magnocellularis (nMAG), one of the avian cochlear nuclei which receive somatic, calyceal innervation from auditory nerve fibres. Whole-cell patch clamp techniques were used to voltage clamp visually identified neurons in brain slices. 2. EPSCs resulting from activation of single axonal inputs were on average -5.3 nA at a driving force of -25 mV. Current-voltage relationships for the peak of the EPSC were linear with a peak conductance of 211 nS. The rate of EPSC decay showed a linear increase with temperature, with a temperature coefficient (Q10) of 2.2 between 25 and 35 degrees C; in vivo (41 degrees C) the EPSC would decay in 0.2 ms. 3. The EPSC was composed of two pharmacologically and kinetically distinct components: an early phase due to non-NMDA (N-methyl-D-aspartate) receptors and a late phase resulting from NMDA receptors. Both components reversed near 0 mV. While both subtypes of glutamate receptor were activated by transmitter, NMDA receptors had a peak conductance at positive potentials which was only 11% of the peak non-NMDA receptor component. 4. EPSCs during trains of stimuli exhibited a progressive decrease in amplitude. The extent of depression increased with the frequency of stimulation and was reduced by drugs which prevent receptor desensitization, indicating that, in part, postsynaptic factors limit synaptic strength during repetitive synaptic activity. Additionally, the coefficient of variation of the EPSC amplitude increased during trains, consistent with presynaptic depression. 5. mEPSCs occurred randomly in the presence of tetrodotoxin and presumably correspond to transmitter quanta. These synaptic events rose (10-90%) within 100 microseconds and decayed with an exponential of 180 microseconds at 29-32 degrees C. Despite the somatic location of the synapse, mEPSCs varied widely in amplitude, suggesting differences in the quantal synaptic current at each synaptic site. The ratio of the average peak conductance of the EPSC and mEPSC gave an estimated quantal content of 103.
 ...
PMID:Voltage clamp analysis of excitatory synaptic transmission in the avian nucleus magnocellularis. 785 16


1 2 Next >>