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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of platelet-activating factor (PAF) on Na(+)-dependent calcium uptake in myocardial sarcolemmal vesicles were examined in order to clarify its mechanism of inotropic action on the heart. PAF (40 and 20 microM) significantly inhibited Na(+)-Ca2+ exchange by 61% and 37%, respectively. Both initial rate of exchange and maximal exchange were inhibited. The Km for the reaction was not altered but Vmax was lowered 55% by PAF. Lyso-PAF inhibited Na(+)-Ca2+ exchange to a similar degree as PAF. CV-3988, a specific PAF receptor antagonist, failed to diminish the inhibitory effect of PAF on Na(+)-Ca2+ exchange, suggesting that the effect of PAF on Na(+)-Ca2+ exchange is not via a receptor mechanism. The passive permeability of sarcolemmal vesicles to Ca2+ was markedly elevated after PAF treatment. However, this effect could not account for the decrease in Na(+)-Ca2+ exchange. Interestingly, passive Ca2+ binding to cardiac sarcolemma was increased by 40 microM PAF. This study indicates that a depression of Na(+)-Ca2+ exchange probably does not play a role in the negative inotropic effect of PAF on the myocardium under physiological conditions. Its mechanism of action on Na(+)-Ca2+ exchange is discussed.
Mol Cell Biochem 1990 Jan 18
PMID:Effect of platelet-activating factor (PAF) on sodium calcium exchange in cardiac sarcolemmal vesicles. 230 77

Platelet-activating factor (PAF) has been implicated as one of the mediators of cardiac anaphylaxis. This phospholipid has been shown to have numerous effects on a variety of tissues, including the heart. Among these effects are alterations in the resting potential and generation of arrhythmias at very low concentrations. This suggests that PAF may modulate the activity of the background, inwardly-rectifying potassium current (IK1). Thus, the effects of PAF on IK1 were examined at the single channel level. Ventricular cells were isolated from adult guinea pig hearts and single channel currents recorded from cell-attached patches. PAF had substantial effects on the single channel currents at sub-nanomolar concentrations (10(-11) to 10(-10) M). PAF initially caused flickering of the channels, followed by a gradual prolonged depression of channel activity. Since these potassium channels play a major role in determining the resting potential and excitability of the cardiac cell, the effects of PAF on IK1 may play a major role in the deleterious electrophysiological actions of PAF on the heart.
Mol Cell Biochem 1990 Mar 05
PMID:Effects of platelet-activating factor on single potassium channel currents in guinea pig ventricular myocytes. 232 95

When perfused with high K+ (8.1 to 14.9 mM)-Tyrode's solution, the upstroke of action potentials in the isolated guinea-pig ventricular muscle is composed of two components and there are two separable peaks in the first derivative, i.e., Vmax, fast and Vmax, slow. The Vmax, fast was a measure of activation of the residual fast channel, while the Vmax, slow was that of the slow channel. Isoproterenol depressed Vmax, fast with increase in Vmax, slow, in a concentration-dependent manner (10(-8) to 10(-6) M). This depression of Vmax, fast was greater at more depolarized levels of membrane potential. Therefore, the isoproterenol-induced depression of Vmax, fast may be due to a negative shift of the curve relating Vmax, fast to the take-off potential (Em) (Vmax--Em relationship), along the voltage axis. The negative shift of Vmax--Em relationship by isoproterenol was also recognized in small preparations the size of which is well within the space constant. The negative shift was inhibited in the presence of beta-blockers (pindolol 1 microgram/ml or atenolol 10 micrograms/ml) but not by a calcium antagonist, 1-verapamil (1 microgram/ml). These results suggest that isoproterenol blocks sodium channels in the depolarized ventricular muscle via stimulation of the beta-adrenoceptors and that the depression of Vmax, fast is not mediated by the well-known effects of isoproterenol on Vmax, slow, i.e., increased influx of Ca2+ ions.
J Mol Cell Cardiol 1985 Jul
PMID:Isoproterenol inhibits residual fast channel via stimulation of beta-adrenoceptors in guinea-pig ventricular muscle. 241 Jun 22

Vmax of the action potential upstroke in canine cardiac Purkinje fibers was studied in the presence of seven class I antiarrhythmic drugs--lidocaine (4 micrograms/ml), mexiletine (4 micrograms/ml), propranolol (0.9 micrograms/ml), procainamide (30 micrograms/ml), quinidine (5 micrograms/ml), flecainide (4 micrograms/ml), and disopyramide (3.1 micrograms/ml)--at constant cycle lengths (CCL) and after abrupt changes in cycle length (ACCL). The time constant of Vmax recovery after ACCL at a basic cycle length of 500 ms was 0.09 +/- 0.01 s for lidocaine, 0.18 +/- 0.03 s for mexiletine, 1.35 +/- 0.20 s for propranolol, 4.4 +/- 0.8 s for procainamide, 8.3 +/- 1.2 s for quinidine, 11.0 +/- 0.9 s for flecainide, and 37.9 +/- 9.4 s for disopyramide. These values were similar to those reported by others in guinea pig papillary muscle, and, with the exception of flecainide, conformed to the scheme proposed by Courtney (J Mol Cell Cardiol 1980; 12:1273-86) based on the molecular weight and lipid solubility hypothesis. Each drug altered the Vmax differently at CCL from after ACCL at the same diastolic intervals. The magnitude of these differences and the range of diastolic intervals at which they were present varied among different drugs. These observations explain differences in the drug effects on the Vmax of the regularly and prematurely occurring depolarizations. In the presence of lidocaine and mexiletine, the recovery kinetics of Vmax were not altered by CCL within the 300-1,500-ms range, and the magnitude of Vmax depression was not influenced by action potential duration within the 200-270-ms range.
 ...
PMID:Frequency-dependent effects of several class I antiarrhythmic drugs on Vmax of action potential upstroke in canine cardiac Purkinje fibers. 241 Jun 78

The secondary amine, mecamylamine, interacts with the nicotinic receptor ionic channel complex as a noncompetitive antagonist. Mecamylamine (1-10 microM) blocked indirect muscle twitches with no discernible effect on the membrane potential, overshoot, or amplitude of the action potential. It also produced a voltage- and concentration-dependent depression of the peak amplitude of the endplate currents (EPC) and induced nonlinearity in the current-voltage relationship. The decay time constant of the EPC (TEPC) was significantly shortened. The linear relationship between the reciprocal of TEPC and the drug concentration suggested an open channel blockade. Patch-clamp studies, in agreement with the noise analysis results, revealed that mecamylamine (1-8 microM) shortened the lifetime of the open channels. Further, the single channel studies showed that at high concentrations mecamylamine reduced the double exponential nature of the distribution of open times characteristic of channels recorded from myoballs. Closed times had a complex distribution that could not be fitted to a single exponential function because of the presence of short closures or "flickers" during the open state. Although the frequency of channel openings progressively decreased with increasing drug concentration, the single channel conductance remained unchanged at all the concentrations tested. Biochemical studies showed that mecamylamine (up to 100 microM) did not block [3H]acetylcholine binding to the nicotinic receptor of the Torpedo electroplax, but inhibited the binding of [3H]perhydrohistionicotoxin to its channel site, both in the resting and the activated state. These results suggested that, at the nicotinic receptors of the neuromuscular junction, mecamylamine acted as a noncompetitive blocker, binding primarily to the receptor's open channel conformation. Most of the alterations of EPCs were consistent with the predictions of a sequential model for open channel blockade. Biochemical and patch-clamp results, however, could not be fully explained by this model and provided some evidence of the existence of additional blocked states most likely through pathways into desensitized species. In contrast to a competitive antagonism of acetylcholine receptors reported at autonomic ganglia, there was no such action of the drug at the neuromuscular junction; thus, mecamylamine is a useful tool to characterize the nicotinic receptors from different synapses.
Mol Pharmacol 1985 Aug
PMID:The acetylcholine receptor of the neuromuscular junction recognizes mecamylamine as a noncompetitive antagonist. 241 Jul 68

The blocking effects of local anesthetics, mexiletine and disopyramide on the sodium currents (INa) of enzymatically isolated, single cells from rat ventricle were studied under voltage clamp conditions. A suction pipette technique was used for voltage clamp and internal perfusion. Potassium currents were blocked by replacing K+ with Cs+ in the internal and external solutions; calcium currents were blocked by replacing Ca2+ with Co2+ in the external solution to isolate INa. When the cells were stimulated infrequently (less than 1 Hz), both drugs produced dose-dependent depression of INa, which was correlated with one-to-one binding to sodium channel. A half-blocking concentration (KD) of 2.8 X 10(-5) M was observed for both agents. The shape of the current-voltage curve along the voltage axis remained unchanged in the presence of either drug. Both drugs shifted the inactivation curve of INa to more negative potentials. Mexiletine produced a marked use-dependent blockage of INa, whereas disopyramide did not produce significant use-dependent block under similar experimental conditions. Both drugs prolonged the recovery of INa from inactivation. The results suggested that both drugs interact with the inactivation mechanism of the sodium channels of rat myocardial cells.
J Mol Cell Cardiol 1985 May
PMID:Blockage of the sodium current in isolated single cells from rat ventricle with mexiletine and disopyramide. 241 42

Using internally dialyzed neurons of Helix, we have examined the effects of sodium-pump activity and intracellular ATP concentration on transmembrane currents induced by acetylcholine (ACh) and gamma-aminobutyric acid (GABA). We also report on the effects of pump activity and levels of intracellular ATP on binding by Helix ganglia of 3H-alpha-bungarotoxin (3H-alpha-BT) and 3H-GABA. Both ouabain-containing and potassium-free solutions depressed the neurotransmitter-induced transmembrane current of one type of dialyzed neurons. An increase in the intracellular ATP concentration led to a depression of ACh-induced currents and to the disappearance of the blocking effect of ouabain on these currents. Intracellular ADP had a similar but smaller effect on transmitter-induced currents, and intracellular AMP was ineffective. The depressing effect of internal ATP on ACh-induced currents was absent in the presence of an inhibitor of membrane phosphorylation (dinitrophenol). The binding of tritium-labeled alpha-BT and GABA to the membranes was depressed by both ouabain-containing and K-free solutions and also by compounds (theophylline and NaF) which increase the levels of intracellular ATP. The results suggest that the Na pump modulates the affinity of ACh and GABA membrane receptors by the regulation of the phosphorylated state of membrane receptors.
Cell Mol Neurobiol 1985 Sep
PMID:Further study of the correlation between Na-pump activity and membrane chemosensitivity. 241 57

Previous experiments showed that the presence of high levels of acute phase reactants (APR) enhance CCl4-induced liver fibrosis in the rat. A high correlation was found between the degree of fibrosis and alpha 2-macroglobulin of the rat (alpha 2-macrofetoprotein, alpha M-FP) used for monitoring the acute phase response. This acute phase reaction was provoked by epinephrine just before CCl4 treatment was started. In the present study we analyzed the effect of APR by repeating these experiments and estimating liver neutral collagenase with a synthetic substrate and endogenous collagen as a substrate, and liver prolyl-4-hydroxylase. A strong depression of liver collagenase activity was found in rats with a preceding acute phase reaction contrary to the rats that underwent CCl4 treatment only. A high level of alpha M-FP correlated negatively with collagenase activity. Also in vitro alpha M-FP proved to inhibit collagenase activity. Prolyl-4-hydroxylase was increased in the rats during acute phase reaction and correlated highly and positively with alpha M-FP, haptoglobin, and ceruloplasmin. Thus high levels of APR promote development of CCl4-induced fibrosis, partly by anticollagenase activity and partly because of enhancement of prolyl-4-hydroxylase activity. The latter phenomenon can also be explained by the presence of APR, but this has to be proved.
Exp Mol Pathol 1986 Oct
PMID:Mechanisms by which acute phase proteins enhance development of liver fibrosis: effects on collagenase and prolyl-4-hydroxylase activity in the rat liver. 242 60

Effects of pentobarbital on the calcium current of Aplysia neurons were investigated under current- and voltage-clamp conditions using the conventional two-microelectrode technique. Pentobarbital attenuated the progressive broadening of repeated action potentials of somata, suggesting a reduction in the calcium current. When calcium ion was replaced with barium ion in the perfusing solution, in which neither sodium nor potassium ions carried transmembrane currents, the barium current (IBa) which flowed through the calcium channel of the cell membrane was generated by depolarizing pulses of several hundred milliseconds applied every 1 min from a holding potential of -50 mV. The IBa was not affected by tetrodotoxin (30 microM). The current was decreased by pentobarbital (0.1-5 mM) in a dose-dependent manner. The inhibition was much greater at a lower pH of the perfusate, indicating that the uncharged form of the agent was responsible. The voltage-dependent inactivation of the IBa proceeded with two time constants [190 +/- 21 and 2020 +/- 146 msec (N = 4) at -10 mV], both of which were shortened by adding 1 mM pentobarbital [to 120 +/- 18 and 540 +/- 51 msec (N = 4), respectively]. The IBa recovered from the inactivation with two time constants [60 +/- 7 and 871 +/- 76 msec (N = 3) at -50 mV]. The anesthetic (1 mM) prolonged both of them, to 124 +/- 20 and 1480 +/- 172 msec (N = 3), respectively, resulting in a use-dependent depression of the current at 2-Hz stimulation. Pentobarbital reduced the IBa to a greater extent when the holding potential was more positive (-30 instead of -50 mV), indicating a higher affinity of the drug to the inactivated state of the channel. These findings suggest that the attenuation of the progressive broadening of successive spikes by pentobarbital is due to a decrease in the voltage- and time-dependent calcium current, ending in depression of transmitter release from the nerve terminal.
Cell Mol Neurobiol 1986 Sep
PMID:Reduction of the voltage-dependent calcium current in Aplysia neurons by pentobarbital. 243 43

The heat shock response was studied as a model for control of gene expression and protein synthesis in Giardia lamblia. Cultured trophozoites were metabolically labelled with [35S]methionine, and proteins were analysed by SDS-polyacrylamide gel electrophoresis and fluorography. A temperature shift from 37 degrees C to 43 degrees C resulted in the depression of normal protein synthesis, and the enhanced synthesis of four major heat shock proteins of 100, 83, 70 and 30 kDa. This response resembles that seen in other organisms of wide phylogenetic diversity. An examination of the kinetics of induction and recovery from heat shock suggests that the individual heat shock proteins are independently regulated. In vitro translation of messenger RNA isolated from heat shocked cells further indicates that regulation occurs at both transcriptional and translational levels. The response of G. lamblia to other stresses including cysteine deprivation, exposure to oxygen, ethanol, hydrogen peroxide, and the chemotherapeutic drugs metronidazole and quinacrine was also investigated. The induction of two or more of the heat shock proteins was generally observed; however, certain treatments inhibited synthesis of all proteins including heat shock proteins.
Mol Biochem Parasitol 1988 Mar
PMID:Heat shock and stress response in Giardia lamblia. 245 80


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