Inhibition by calcium channel blockers of the glycogenolytic effect of glucagon in perfused rat liver

1982 ◽  
Vol 99 (4) ◽  
pp. 559-566 ◽  
Author(s):  
Satoshi Kimura ◽  
Toshio Matsumoto ◽  
Ryoko Tada ◽  
Etsuro Ogata ◽  
Kaoru Abe
Keyword(s):  
Cyclic Amp ◽  
Calcium Channel ◽  
Rat Liver ◽  
Calcium Channel Blockers ◽  
Calcium Influx ◽  
Extracellular Calcium ◽  
Channel Blockers ◽  
Perfused Rat Liver ◽  
Glycogenolytic Effect ◽  
Glucose Output

Abstract. Verapamil and diltiazem, calcium channel blockers, inhibited significantly the glucagon-induced glucose output and 45Ca efflux from perfused rat liver at concentrations higher than 50 μm when the perfusate contained calcium. Although the blockers partially interfered with glucagon-induced elevation of cyclic AMP in the tissue, they also inhibited the effects of cyclic AMP. The blockers did not show the inhibitory effects in the absence of perfusate calcium. However, the inhibition of calcium influx into hepatocytes by omission of extracellular calcium or addition of EGTA did not interfere with these effects of glucagon and cyclic AMP. In the presence of extracellular calcium, the blockers did not inhibit cyanide-induced glucose output, indicating that the activity of glycogen phosphorylase and later processes leading to glucose output were not affected by the blockers. These data suggest that, in the presence of calcium, the blockers inhibit the effect of glucagon also at a step (or steps) subsequent to cyclic AMP production and before the activation of phosphorylase b, probably by inhibiting glucagon-induced mobilization of calcium from intracellular calcium pools rather than inhibiting calcium influx into hepatocytes.

Spike aftercurrents in R15 of Aplysia: their relationship to slow inward current and calcium influx

1984 ◽  
Vol 51 (2) ◽  
pp. 387-403 ◽  
Author(s):  
D. V. Lewis
Keyword(s):  
Calcium Channel ◽  
Intracellular Calcium ◽  
Calcium Channel Blockers ◽  
Calcium Influx ◽  
Extracellular Calcium ◽  
Slow Inward Current ◽  
Extracellular Potassium ◽  
Channel Blockers ◽  
Tetraacetic Acid ◽  
Inward Current

Spikes in the bursting neuron, R15, are followed by depolarizing afterpotentials (35) and often by delayed hyperpolarizing afterpotentials as well. Placing the cell in a voltage clamp after a spike allows measurement of the depolarizing aftercurrent (DAC) and hyperpolarizing aftercurrent (HAC) that underlie the afterpotentials. Subthreshold depolarizations give rise to small DACs and HACs. The DAC and the slow inward current (SIC) of R15 are reduced or blocked in a similar manner by many experimental manipulations, e.g., application of dopamine, zero-calcium seawater, zero-sodium seawater, or calcium-channel blockers (Mn2+ and La3+), or cooling the cell from 21-22 degrees C to 10 degrees C. Neither the DAC nor the SIC were blocked by tetrodotoxin (100 uM) and neither was sensitive to altered extracellular potassium. Both the DAC and SIC become larger as the holding potential of the cell is progressively depolarized from -70 to -40 mV. DACs are sensitive to the injection of intracellular calcium chelators (EGTA (ethylene glycol-bis(beta-aminoethyl ether)-N,N1-tetraacetic acid) or EDTA [ethylenedinitrilo)tetraacetic acid]. DAC amplitude is approximately 90% reduced by intracellular EGTA concentration near 1mM. In contrast, the SIC is unchanged or much less affected by the calcium buffers. DACs are also more sensitive to low (1 mM) extracellular calcium than is the SIC. The HAC is also a calcium-dependent current. It is blocked by any experimental manipulation reducing calcium influx or intracellular calcium accumulation, i.e., reduced extracellular calcium, calcium-channel blockers, or intracellular EGTA. We suggest that the DAC and the SIC are carried by the same conductance mechanism. In the case of the DAC, the conductance might be activated by a rise in intracellular calcium activity accompanying the spike and, in the case of the SIC, depolarization per se may be the most important activating condition.

scholarly journals A Systematic Review on 1, 4-Dihydropyridines and its Analogues: An Elite Scaffold

2021 ◽  
Vol 12 (3) ◽  
pp. 3117-3134
Keyword(s):  
Myocardial Infarction ◽  
Systematic Review ◽  
Clinical Trials ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Calcium Influx ◽  
Channel Blockers ◽  
Neuroprotective Effects ◽  
Dihydropyridine Derivatives

1,4-Dihydropyridines are a group of pyridine-based molecules possessing a magnificent set of biological and therapeutic potentials. Belonging to the class of calcium channel blockers, they are known to be effective in the conditions, angina, hypertension, myocardial infarction and show vasodilatory and cardiac depressant effects. Hypotensive, antimicrobial, anticancer, anticoagulant, antioxidant, anticonvulsant, antimalarial, antiulcer, and neuroprotective effects have been reported with their rational use. The effects are precipitated in response to inhibition of calcium channels, gradually restricting calcium influx. Drugs like nifedipine, felodipine, and amlodipine are commonly used clinically. Several other drugs belonging to this class have been under clinical trials. The present review focuses on the various 1,4-dihydropyridine derivatives and their pharmacological actions.

scholarly journals Calcium channel blockers do not protect against saturated fatty acid-induced ER stress and apoptosis in human pancreatic β-cells

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Jan Šrámek ◽  
Vlasta Němcová ◽  
Jan Kovář
Keyword(s):  
Er Stress ◽  
Calcium Channel ◽  
Cell Lines ◽  
Calcium Channel Blockers ◽  
Calcium Influx ◽  
Saturated Fatty Acids ◽  
Channel Blockers ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

AbstractIt was evidenced that saturated fatty acids (FAs) have a detrimental effect on pancreatic β-cells function and survival, leading to endoplasmic reticulum (ER) calcium release, ER stress, and apoptosis. In the present study, we have tested the effect of three calcium influx inhibitors, i.e., diazoxide, nifedipine, and verapamil, on the apoptosis-inducing effect of saturated stearic acid (SA) in the human pancreatic β-cell lines NES2Y and 1.1B4. We have demonstrated that the application of all three calcium influx inhibitors tested has no inhibitory effect on SA-induced ER stress and apoptosis in both tested cell lines. Moreover, these inhibitors have pro-apoptotic potential per se at higher concentrations. Interestingly, these findings are in contradiction with those obtained with rodent cell lines and islets. Thus our data obtained with human β-cell lines suggest that the prospective usage of calcium channel blockers for prevention and therapy of type 2 diabetes mellitus, developed with the contribution of the saturated FA-induced apoptosis of β-cells, seems rather unlikely.

Calcium influx regulates antibody-induced glycoprotein movements within the Chlamydomonas flagellar membrane

1990 ◽  
Vol 96 (1) ◽  
pp. 27-33 ◽  
Author(s):  
R.A. Bloodgood ◽  
N.L. Salomonsky
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Calcium Influx ◽  
Gliding Motility ◽  
Free Calcium ◽  
Membrane Glycoprotein ◽  
Channel Blockers ◽  
Membrane Glycoproteins ◽  
Whole Cell ◽  
Flagellar Membrane

The Chlamydomonas flagellar surface exhibits a number of dynamic membrane phenomena associated with whole-cell gliding locomotion and the early events in fertilization. Crosslinking of a specific population of flagellar surface-exposed glycoproteins with the lectin concanavalin A or an anti-carbohydrate mouse monoclonal antibody, designated FMG-1, results in a characteristic pattern of glycoprotein redistribution within the plane of the flagellar membrane. Recent evidence suggests that flagellar membrane glycoprotein movements are associated with both whole-cell gliding motility and the early events in mating. It is of interest to determine the transmembrane signaling pathway whereby crosslinking of the external domains of flagellar glycoproteins activates the intraflagellar machinery responsible for translocation of flagellar membrane glycoproteins. The redistribution of flagellar membrane glycoproteins requires micromolar levels of free calcium in the medium; lowering the free calcium concentration to 10(−7) M results in complete but reversible inhibition of redistribution. Redistribution is maximal in the presence of 20 microM free calcium in the medium. Redistribution is inhibited in the presence of 20 microM free calcium by the calmodulin antagonists trifluoperazine, W-7 and calmidazolium, the calcium channel blockers diltiazem, methoxyverapamil (D-600) and barium chloride, and the local anesthetics, lidocaine and procaine. The actions of all of these agents can be interpreted in terms of a requirement for calcium in the signaling mechanism associated with flagellar glycoprotein redistribution. In particular, the requirement for micromolar calcium in the external medium and the effects of specific calcium channel blockers suggest that flagellar membrane glycoprotein crosslinking may induce an increase in calcium influx, which may be the initial trigger for activating the flagellar machinery responsible for active movement of flagellar membrane glycoproteins.

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