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)

In trachea bathed by Krebs solution containing indomethacin 0.8 mumol l-1, Bay K 8644 (0.01-1 mumol l-1) evoked mild spasm. Peak tension was achieved after 10 min and was generally less than 20% of an acetylcholine (ACh) maximum. The effect of Bay K 8644 was not potentiated by addition of 2.5 mmol l-1 potassium chloride (KCl) to the Krebs solution. Bay K 8644 (1 mumol l-1) caused a small potentiation of KCl and tetraethylammonium (TEA). In contrast it did not modify the actions of ACh or histamine. Bay K 8644 (1 mumol l-1) caused a small potentiation of the effect of calcium chloride (CaCl2) tested in trachea bathed by a K+-rich, Ca2+-free, MOPS-buffered physiological salt solution. Organic inhibitors of calcium influx such as nifedipine (0.1 mumol l-1), verapamil (1 mumol l-1) or diltiazem (10 mumol l-1) each caused marked depression of concentration-effect curves to KCl. Bay K 8644 (0.01-1 mumol l-1) provided concentration-dependent protection against this effect in all three cases. Estimation of calcium influx by the lanthanum technique revealed that Bay K 8644 (1 mumol l-1) was able to promote the cellular influx of Ca2+. Intracellular electrophysiological recording showed that Bay K 8644 (1 mumol l-1) caused no change in the resting membrane potential of trachealis cells and no change in the properties of the spontaneous electrical slow waves. However, Bay K 8644 was able to delay the slow wave suppression evoked by 1 mumol l-1 nifedipine. The ability of Bay K 8644 to promote Ca2+ influx and its ability to protect against the effects of several structurally-unrelated inhibitors of Ca2+ influx are consistent with Bay K 8644 acting as an agonist at the dihydropyridine receptor associated with the voltage-operated Ca2+ channel (VOC) of trachealis muscle. By this action it potentiates those spasmogens (KCl, TEA) which act by permitting Ca2+ influx through VOCs. In contrast it has no effect on those spasmogens (ACh, histamine) which principally act to liberate Ca2+ from intracellular sites of sequestration.
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PMID:The effects of the dihydropyridine Bay K 8644 in guinea-pig isolated trachealis. 241 35

The effect on the afferent synaptic transmission of Ba2+, Sr2+, tetraethylammonium (TEA) and 4-aminopyridine (4-AP) has been investigated in the isolated frog labyrinth by intracellularly recording the posterior canal resting and evoked receptor discharge. BaCl2 (0.3 mM) or SrCl2 (1.8 mM) substitution for normal external CaCl2 restored the afferent activity without affecting the membrane potential of the sensory fibres. On further increasing Ba2+ concentration (0.5-5 mM) a dose-dependent increase in the EPSP and spike discharges was observed in all the units examined. Ba2+ (1.8-4 mM) removed the depression of the sensory activity operated by CoCl2 (3 mM), while its facilitatory effect was completely antagonized by raising Ca2+ concentration (up to 10 mM). TEA (20 mM) elicited a clear-cut increase in the EPSP and spike discharges which, however, was less consistent than that produced by Ba2+ (1 mM). The increment in spike frequency produced by TEA and Ba2+ proved to be inversely related to the initial resting firing level of the different units. The 4-AP (4-20 mM) effect resulted in a decrease of the sensory activity, which was fully restored by TEA or Ba2+. In normal saline a linear relationship was found between the mean unit resting discharge and the respective excitatory peak response during sinusoidal rotation (0.1-0.3 Hz). This result suggest that the mechanical response is mainly determined by the unit resting level. Consistent evoked responses were obtained under TEA and Ba2+ treatment which proved to depend linearly on the new mean resting discharge of the different units. Conversely, a reduced evoked response was invariably observed in all the fibres tested in the presence of 4-AP. The present results suggest that Ba2+ and Sr2+ may substitute for Ca2+ in the transmitter release process at the cyto-neural junction, the ability of Ba2+ being even larger than that of Sr2+ and Ca2+ itself. The effects of TEA and 4-AP are discussed in the light of their possible interaction with the presynaptic K+-currents recently described in hair cells.
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PMID:The effect of barium and some channel blockers on sensory discharge of the frog labyrinth posterior canal recorded at rest and during rotation. 245 27

To obtain information on the sites and mechanisms of the myoneural effect of aminoglycoside and polypeptide type antibiotics, the influence of neomycin, streptomycin, gentamicin and polymyxin B on the depression of the force of contraction (P) of the rat phrenic nerve-hemidiaphragm preparation was investigated at 37 degrees C, 27 degrees C or 17 degrees C and also at 37 degrees C in electrolyte solutions containing 2.5, 1.25 or 0.625 mM CaCl2. Decreasing the temperature or the CaCl2 concentration ((CaCl2)o) of the bath significantly (p less than 0.001) decreased P. The depressant effect of aminoglycosides on P (about 50% of control at 17 degrees C) was increased more with lower temperatures than that of polymyxin B (about 20%). The effect of lowering the (CaCl2)o on the depression of P (about 90% of control at the lowest (CaCl2)o) was about the same with the 4 antibiotics. The development of the maximal effect and the recovery of P after washout was slower with polymyxin B than with the 3 aminoglycosides. 4-Aminopyridine antagonized the depression of P caused by polymyxin B less than that caused by aminoglycosides. The findings suggest that aminoglycosides depress myoneural activity primarily by inhibiting stimulated release of ACh. Polymyxin B also inhibits ACh release, but inhibition of the contraction of myofibrils contributes more significantly to its myoneural effects than with aminoglycosides. It is conceivable that blocking of the ionophores of the postjunctional membrane also contributes to the myoneural effects of polymyxin B.
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PMID:The influence of temperature and calcium concentration on the myoneural effect of antibiotics. 252 Mar 55

The efficiency of transferring the total energy generated by ventricular contraction (pressure-volume area, PVA) to external work (EW) and internal work (IW) and the myocardial oxygen consumption (MVO2) at zero PVA were determined during volume loading on right heart bypass before and after a 50% augmentation (CaCl2, 0.03 mEq/kg/min, n = 7) or depression (20 minutes of 37 degrees C ischemia with 30 minutes of reperfusion, n = 7) of the contractile state. An increased EW efficiency (64% +/- 7% vs. 81% +/- 6%, p less than 0.01) with reciprocally decreased IW efficiency (36% +/- 7% vs. 19% +/- 6%, p less than 0.01) occurs with calcium chloride-augmented contractility. A reversible ischemia and reperfusion insult has the converse effect on these relative efficiencies (EW, 73% +/- 4% vs. 49% +/- 4%; IW, 27% +/- 4% vs. 51% +/- 4%; each p less than 0.01). Calcium chloride increases the oxygen requirements of both basal metabolism (28 +/- 2 vs. 67 +/- 9 ml O2/beat/100 gm LV, p less than 0.01) and fiber shortening (11 +/- 5 vs. 62 +/- 11 ml O2/beat/100 gm LV, p less than 0.01). The postischemic heart has a decreased oxygen need for shortening (20 +/- 2 vs. 3 +/- 4 ml O2/beat/100 gm LV, p less than 0.01), paralleling the depressed inotropic state. This new model of compartmentalized chemomechanical transduction may allow specific modulation of the energetic derangements attendant to the surgically treated heart.
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PMID:Compartmentalizing chemomechanical transduction in the ejecting heart. 276 28

Using a radiolabelling technique it was possible to measure changes of cholinergic nerve activity in human isolated taenia coli muscle. Loperamide (1.9-97.3 microM) depressed release of acetylcholine produced by electrical field stimulation to a greater degree than morphine (0.13-130 microM). The effect of loperamide was only partially sensitive to naloxone. Loperamide (7.8 microM) demonstrated calcium channel blocking-like properties as shown by its antagonism of CaCl2-induced contractions of depolarised muscle. Although an established calcium channel antagonist, verapamil, was also able to depress cholinergic nerve activity, the concentration was considerably greater than required for antagonism of CaCl2 contractions. The depression of acetylcholine release by loperamide may contribute to its anti-diarrhoeal properties.
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PMID:Opioid and non-opioid actions of loperamide on cholinergic nerve function in human isolated colon. 285 Feb 1

1. The preceding paper (Van der Kloot, 1988) described a method for estimating the timing of quantal releases during an end-plate current. This period of elevated quantal release is called the early release period or ERP (Barrett & Stevens, 1972b). In the present paper, this deconvolution method is used to study the effects of varying quantal output by extracellular ions, stimulus patterns and drugs. 2. The data were obtained by voltage clamping end-plates in low-Ca2+ high-Mg2+ solutions, or in solutions containing tubocurarine (measuring the decay of the miniature end-plate currents (MEPCs) before curarization and assuming a value for MEPC amplitude after curarization). Data were also obtained by extracellular recording in Ca2+-free solution, using a recording pipette filled with CaCl2 and regulating Ca2+ release with a bias current. The three approaches led to similar conclusions. 3. Quantal release rose during the ERP along a sigmoid curve and reached a maximum after about 1.4 ms at 10 degrees C. This is called the time to peak. Quantal release then fell, following an exponential time course with a time constant of about 1.2 ms (10 degrees C). This is called the time constant for decline. 4. The ERP was followed by further, elevated quantal release, at a much lower rate, which declined over a longer time course. This is called late release. The magnitude of late release appears to be almost independent of the magnitude of release during the ERP, although the deconvolution method is a poor one for determining late release. The remainder of the results therefore focus on the ERP. 5. Increasing [Ca2+]o increased quantal output, and the rate of quantal output. It did not change the time to peak or the time constant of decline. Similarly, replacing Ca2+ with Sr2+ did not alter the time course of the ERP. 6. Two-pulse facilitation increased quantal output without changing the time to peak or the time constant of decline. 7. Quantal output was enhanced still more following a brief series of repetitive nerve stimulations. There was a lengthening of the time to peak; there was no change in the decline. The depression produced by longer series of repetitive stimulations did not change the time course of the ERP. 8. 4-Aminopyridine (4-AP) and dimethylsulphoxide (DMSO) increased quantal output and lengthened the time to peak, without altering the time constant for decline. 9. Adenosine decreased quantal output without altering the time course of the ERP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The kinetics of quantal releases during end-plate currents at the frog neuromuscular junction. 285 24

Isolated tracheal strip-chain preparation of the guinea-pig was used to study the effect of temperature on carbachol-induced contraction. The preparation was suspended in the organ bath containing Krebs bicarbonate solution for isometric tension recording. A decrease of bath temperature from 37 degrees C to 20 degrees C (cooling) caused a transient increase in tension and thereafter inhibited the contractile response of the trachea caused by carbachol (30 nmol/l-3 mumol/l). Isosmotic potassium chloride (KCl, 64.7 mmol/l)-induced contraction or calcium chloride (CaCl2, 0.1--3 mmol/l)-induced contraction in K+-depolarized muscle was markedly inhibited by cooling. Verapamil in concentrations of 1 mumol/l or greater, which markedly depressed the CaCl2-induced contraction, caused partial depression of the contractile response to carbachol. On the other hand, carbachol-induced contraction of the trachea which was incubated with K+-rich, verapamil (3 mumol/l) containing Krebs solution and with Ca2+-free, EGTA (0.4 mmol/l) containing Krebs solution were both augmented at 20 degrees C. From these observations, it is concluded that decreased responsiveness of the guinea-pig airway smooth muscle to carbachol with lowered temperature may be due to an inhibition of Ca2+ influx through voltage-dependent Ca2+ channels which involves part of the contraction.
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PMID:Cooling-induced subsensitivity to carbachol in the tracheal smooth muscle of the guinea-pig. 287 96

In an attempt to elucidate the mechanism of inhibitory action of oxatomide on smooth muscle against various spasmogens, we studied the effect of this drug on cumulative dose response curves (CDRC) to CaCl2 in guinea pig ileum. We found that oxatomide induces a shift to right and a non-surmountable depression of the maximal response of these CDRC which suggests non-competitive antagonism. Furthermore, oxatomide inhibits 45Ca2+ uptake by guinea pig ileum after acetylcholine stimulation which constitutes strong evidence that inhibition of calcium ion utilization by smooth muscle cells plays a major role in the mode of action of oxatomide.
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PMID:Effect of oxatomide on calcium ions in smooth muscle. 287 34

Experiments were carried out in-vitro using segments of guinea-pig ileum, taenia caeci, ureter and detrusor. In the ileum, oxybutynin (30, 100 nM) competitively antagonized acetylcholine-induced contractions but did not alter those induced by histamine. Higher concentrations of oxybutynin (up to 10 microM) induced a non-competitive depression of responses to both agonists and caused a parallel shift to the right of the Ca2+-induced contractions in taenia caeci strips bathed in a Ca2+-free, high-K+ medium. In the ureter, oxybutynin (1-10 microM) impaired rhythmic muscular contractions in normal medium and after CaCl2 addition in Ca2+-free medium. Similarly to verapamil (10, 30 microM), oxybutynin (10, 30 microM) depressed both the cholinergic and non-adrenergic, non-cholinergic components of the electrically-induced contractions of detrusor strips. It is concluded that oxybutynin has anticholinergic properties and, at higher concentrations, exerts a direct spasmolytic activity possibly mediated by blockade of the transmembrane Ca2+ fluxes responsible for smooth muscle contraction.
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PMID:Depressant action of oxybutynin on the contractility of intestinal and urinary tract smooth muscle. 288 93

ATPase and calcium binding activities were studied in sarcolemmal membranes from hearts of male rats fed either a control or 2% cholesterol diet for different time periods. Studies with isolated membrane revealed a significant increase in Na+-K+ ATPase activity, sialic acid content and ATP-independent calcium binding capacity in the presence of 1.25 mM CaCl2 in the 6 week cholesterol fed group. By 12 weeks, Na+-K+ ATPase, Mg2+-ATPase and Ca2+-ATPase activities as well as ATP-independent calcium binding in the presence of 0.05 mM CaCl2 were increased in membranes from cholesterol fed rats. A significant increase (P less than 0.05) in the sarcolemmal cholesterol/phospholipid molar ratio, which is an indicator of a decrease in membrane fluidity, was also noted in the 12 week cholesterol fed group. Concanavalin A, which is believed to decrease membrane fluidity, stimulated both Mg2+ and Ca2+-dependent ATPase activities and increased ATP-independent calcium binding in control sarcolemmal preparations and these changes resembled those observed in the sarcolemma from cholesterol fed rats. Since concanavalin A did not alter the activity of Na+-K+ ATPase, it appears that some of the observed differences in sarcolemmal activities upon cholesterol feeding did not correlate well with changes in membrane order. At 24 weeks, there was a generalized depression in the sarcolemmal ATPase activities of the cholesterol group; both Mg2+ ATPase and Ca2+ ATPase were significantly less than in control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heart sarcolemmal ATPase and calcium binding activities in rats fed a high cholesterol diet. 299 27


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