Dihydropyridine Modulation of Voltage‐Activated Calcium Channels in PC12 Cells: Effect of Pertussis Toxin Pretreatment

Schettini, Gennaro; Meucci, Olimpia; Grimaldi, M.; Florio, Tullio; Landolfi, E.; Scorziello, Antonella; Ventra, C.

doi:10.1111/j.1471-4159.1991.tb01995.x

Cited by 11 publications

(4 citation statements)

References 24 publications

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“…In this series of experiments the [ 3 H]-thymidine incorporation assay was tested after only one day of treatment, due to the potential toxicity of the inhibitors used. The increase in DNA synthesis and proliferative activity induced by PrP 106±126 was completely blocked by the pretreatment with nicardipine [38], an L-type voltage-sensitive calcium channel (VSCC) blocker, while KT-5720, an inhibitor of the protein kinase A (PKA), vanadate, an inhibitor of phosphotyrosine phosphatases and MK801, a selective inhibitor of the NMDA receptor-gated calcium channel, resulted ineective (Table 1).…”

Section: Prp 106±126-induced Astrocytes Proliferationmentioning

confidence: 99%

Intracellular mechanisms mediating the neuronal death and astrogliosis induced by the prion protein fragment 106–126

Thellung

Florio

Corsaro

et al. 2000

Intl J of Devlp Neuroscience

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Prion encephalopathies include fatal diseases of the central nervous system of men and animals characterized by nerve cell loss, glial proliferation and deposition of amyloid fibrils into the brain. During these diseases a cellular glycoprotein (the prion protein, PrP(C)) is converted, through a not yet completely clear mechanism, in an altered isoform (the prion scrapie, PrP(Sc)) that accumulates within the brain tissue by virtue of its resistance to the intracellular catabolism. PrP(Sc) is believed to be responsible for the neuronal loss that is observed in the prion disease. The PrP 106-126, a synthetic peptide that has been obtained from the amyloidogenic portion of the prion protein, represents a suitable model for studying the pathogenic role of the PrP(Sc), retaining, in vitro, some characteristics of the entire protein, such as the capability to aggregate in fibrils, and the neurotoxicity. In this work we present the results we have recently obtained regarding the action of the PrP 106-126 in different cellular models. We report that the PrP 106-126 induces proliferation of cortical astrocytes, as well as degeneration of primary cultures of cortical neurons or of neuroectodermal stable cell lines (GH(3) cells). In particular, these two opposite effects are mediated by the same attitude of the peptide to interact with the L-type calcium channels: in the astrocytes, the activity of these channels seems to be activated by PrP 106-126, while, in the cortical neurons and in the GH(3) cells, the same treatment causes a blockade of these channels causing a toxic effect.

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Section: Prp 106±126-induced Astrocytes Proliferationmentioning

confidence: 99%

Intracellular mechanisms mediating the neuronal death and astrogliosis induced by the prion protein fragment 106–126

Thellung

Florio

Corsaro

et al. 2000

Intl J of Devlp Neuroscience

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“…PC 12 cells are more uniform than primary culture cells, which makes it easier to select cells and to draw generalized conclusions. The presence of Ca2~channels in PC12 cells is well documented (Plummer et al, 1989;Streit and Lux, 1990;Reber and Reuter, 1991;Schettini et al, 1991;Meucci et al, 1992). Although derived from pheochromocytoma cells, they express N channels, which are regarded to be neuron-specific and are important in the control of neurotransmitter release (Plummer et al, 1989;Usowicz et al, 1990).…”

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confidence: 99%

Selective Changes in Cell Bodies and Growth Cones of Nerve Growth Factor‐Differentiated PC12 Cells Induced by Chemical Hypoxia

Gibson

Toral‐Barza

Zhang

1997

Journal of Neurochemistry

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Cytosolic free Ca 2~concentration ([Ca2~]) was measured in differentiated PCi 2 cells to test whether chemical hypoxia selectively alters intracellular Ca2~in growth cones and cell bodies. Hypoxia increased [Ca2~] 1 and exaggerated its response to Kdepolarization in both parts of the cells. [Ca 2~]ĩn the cell bodies was greater than that in the growth cones under resting conditions and in response to Kõr hypoxia. Ca2-channel blockers selectively altered these responses. The L-channel blocker nifedipine reduced [Ca2~]following Kdepolarization by 67% in the cell bodies but only 25% in the growth cones. In contrast, the N-channel blocker w-conotoxin GVIA (w-CgTX) diminished K~-inducedchanges in [Ca2~] 1 only in the growth cones. During hypoxia, nifedipine was more effective in the cell bodies than in the growth cones. During hypoxia, w-CgTX diminished K~induced changes by 50-75% in both parts of the cell, but only immediately after depolarization. The combination of nifedipine and w-CgTX diminished the [Ca 2~]response to Kwith or without hypoxia by >90% in the cell body and 70% in the growth cones. Thus, the increased Ca2 entry with Kduring hypoxia is primarily through L channels in the cell bodies, whereas in growth cones influx through L and N channels is about equal. The results show that chemical hypoxia selectively alterIba2+ regulation in the growth cone and cell body of the same cell.

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“…These results c o n k our previous observation in a pituitary tumor-derived cell line (235-1 cells) in which PTX pretreatment abolished nicardipine inhibition of the MTX-induced increase in the intracellular calcium level . However, PTX does not modify the Bay K 8644 potentiation of the MTX effect on the cytosolic calcium (data not shown), whereas it was able to reduce Bay K 8644 enhancement of potassium-depolarization induced calcium rise in PC12 (Schettini et al, 1991). Also the inhibitory effect of w-CgTx on MTXinduced calcium influx disappeared in PTX-treated cells.…”

Section: Discussionmentioning

confidence: 86%

“…The cytosolic free calcium concentration was measured by means of the fluorescent probe fura 2 (Calbiochem) as previously described by Schettini et al (1991). PC12 cells were detached from the culture flasks by using a 0.05% trypsin/0.02% EDTA mixture (Flow), washed twice in serumfree RPMI, and finally resuspended 2 x 106/ml in the same medium.…”

Section: Cytosolic Free Calcium Measurementmentioning

confidence: 99%

Maitotoxin‐Induced Intracellular Calcium Rise in PC 12 Cells: Involvement of Dihydropyridine‐Sensitive and ω‐Conotoxin‐Sensitive Calcium Channels and Phosphoinositide Breakdown

Meucci

Grimaldi

Scorziello

et al. 1992

Journal of Neurochemistry

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The biological activities of maitotoxin are strictly dependent on the extracellular calcium concentration and are always associated with an increase of the free cytosolic calcium level. We tested the effects of voltage-sensitive calcium channel blockers (nicardipine and omega-conotoxin) on maitotoxin-induced intracellular calcium increase, membrane depolarization, and inositol phosphate production in PC12 cells. Maitotoxin dose dependently increased the cytosolic calcium level, as measured by the fluorescent probe fura 2. This effect disappeared in a calcium-free medium; it was still observed in the absence of extracellular sodium and was enhanced by the dihydropyridine calcium agonist Bay K 8644. Nicardipine inhibited the effect of maitotoxin on intracellular calcium concentration in a dose-dependent manner. The maitotoxin-induced calcium rise was also reduced by pretreating cells with omega-conotoxin. Pretreatment of cells with maitotoxin did not modify 125I-omega-conotoxin and [3H]PN 200-110 binding to PC12 membranes. Nicardipine and omega-conotoxin inhibition of maitotoxin-evoked calcium increase was reduced by pertussis toxin pretreatment. Maitotoxin caused a substantial membrane depolarization of PC12 cells as assessed by the fluorescent dye bisoxonol. This effect was reduced by pretreating the cells with either nicardipine or omega-conotoxin and was almost completely abolished by the simultaneous pretreatment with both calcium antagonists. Maitotoxin stimulated inositol phosphate production in a dose-dependent manner. This effect was reduced by pretreating the cells with 1 microM nicardipine and was completely abolished in a calcium-free EGTA-containing medium. The findings on maitotoxin-induced cytosolic calcium rise and membrane depolarization suggest that maitotoxin exerts its action primarily through the activation of voltage-sensitive calcium channels, the increase of inositol phosphate production likely being an effect dependent on calcium influx. The ability of nicardipine and omega-conotoxin to inhibit the effect of maitotoxin on both calcium homeostasis and membrane potential suggests that L- and N-type calcium channel activation is responsible for the influx of calcium following exposure to maitotoxin, and not that a depolarization of unknown nature causes the opening of calcium channels.

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Dihydropyridine Modulation of Voltage‐Activated Calcium Channels in PC12 Cells: Effect of Pertussis Toxin Pretreatment

Cited by 11 publications

References 24 publications

Intracellular mechanisms mediating the neuronal death and astrogliosis induced by the prion protein fragment 106–126

Intracellular mechanisms mediating the neuronal death and astrogliosis induced by the prion protein fragment 106–126

Selective Changes in Cell Bodies and Growth Cones of Nerve Growth Factor‐Differentiated PC12 Cells Induced by Chemical Hypoxia

Maitotoxin‐Induced Intracellular Calcium Rise in PC 12 Cells: Involvement of Dihydropyridine‐Sensitive and ω‐Conotoxin‐Sensitive Calcium Channels and Phosphoinositide Breakdown

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