Pertussis toxin pretreatment abolishes dihydropyridine inhibition of calcium flux in the 235-1 pituitary cell line

Schettini, Gennaro; Meucci, Olimpia; Florio, Tullio; Grimaldi, M.; Landolfi, E.; Magri, Geo; Yasumoto, Takeshi

doi:10.1016/0006-291x(88)90602-x

Cited by 10 publications

(3 citation statements)

References 24 publications

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“…A direct correlation between a PTX-sensitive G protein and the effect of nicardipine on activated calcium channels cannot be ruled out completely. We previ-ously observed that PTX pretreatment reduced nicardipine inhibition of the intracellular calcium rise caused by maitotoxin (Schettini et al, 1988;Meucci et al, 1989), a potent calcium channel activator, in different cell types (Takahashi and Ohizumi, 1982;Takahashi et al, 1983;Freedman et al, 1984;Schettini et al, 1984). Because the effect of maitotoxin on calcium channels was not affected by PTX pretreatment, the reduction of the effect of nicardipine could be ascribed to the involvement of a G protein in the dihydropyridine interaction with the maitotoxin-activated form of the calcium channel (Schettini et al, 1988).…”

Section: Discussionmentioning

confidence: 89%

“…Electrophysiological evidence, along with binding studies, also suggests that a G protein could modulate the activity of L-type channel in neuronal tissues (Scott and Dolphin, 1987;Bergamaschi et al, 1989). Furthermore, we have reported previously that a pertussis toxin (PTX)-sensitive G protein could be involved in modulating the inhibition of nicardipine on maitotoxin-activated calcium channels in a clonal pituitary cell line (235-1 cells) (Schettini et al, 1988).…”

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confidence: 99%

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

Schettini

Meucci

Grimaldi

et al. 1991

Journal of Neurochemistry

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In this study, we report the effect of pertussis toxin pretreatment on dihydropyridine modulation of voltage-sensitive calcium channels in PC12 cells. The rise in intracellular calcium concentration caused by potassium depolarization is not affected significantly by pertussis toxin pretreatment. Nicardipine, a dihydropyridine derivative, added either before or after potassium-induced depolarization, reduces the resultant elevation in cytosolic calcium level both in control and in pertussis toxin-treated cells. The dihydropyridine agonist Bay K 8644, when added before potassium, is able to enhance the potassium-induced spike of cytosolic calcium levels, an effect significantly reduced by pertussis toxin pretreatment. Moreover, the addition of Bay K 8644 after potassium holds the intracellular calcium concentration at a cytosolic sustained level during the slow inactivating phase of depolarization. This effect of Bay K 8644 is inhibited by nicardipine. Pertussis toxin pretreatment slightly weakens the effect of Bay K 8644 when added after potassium-induced depolarization, whereas it significantly reduces the nicardipine inhibition of cytosolic calcium rise stimulated by potassium and Bay K 8644, but not by potassium alone. In conclusion, our findings suggest that a pertussis toxin-sensitive guanine nucleotide regulatory protein could be involved in the interaction between dihydropyridine derivatives and voltage-dependent calcium channels.

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Section: Discussionmentioning

confidence: 89%

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confidence: 99%

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

Schettini

Meucci

Grimaldi

et al. 1991

Journal of Neurochemistry

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“…These results show that MTX-induced membrane depolarization is dependent on the passage of calcium through VSCC and not that a depolarization of unknown nature induces the openings of VSCC. The possible involvement of a PTX-sensitive G protein in the interaction of MTX with VSCC was considered in light of the growing evidence concerning the role of G proteins in the regulation of ion channel activity Schettini et al, 1988;Schultz et al, 1990;Bergamaschi et al, 1990). Under our conditions, because PTX pretreatment does not significantly modify the effect of MTX on calcium rise , a G protein sensitive to PTX does not seem to be involved directly in MTX interaction with VSCC.…”

Section: Discussionmentioning

confidence: 90%

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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Charge movement and calcium currents in skeletal muscle fibers are enhanced by GTP?S

1990

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G-proteins play several regulatory roles in the cell. They can modulate ionic channels directly or in association with second messengers. In skeletal muscle, G-proteins modulate the activity of calcium channels either by acting directly on the channel and/or through a cAMP-dependent phosphorylating mechanism. The activation of G-proteins by GTP gamma S can also induce force generation in skinned fibers. In this paper we studied the effect of GTP gamma S on charge movement and calcium currents (ICa) in rat and frog skeletal muscle, using the Vaseline gap technique. We observed an increase in both charge movement and ICa after the intracellular addition of 10-100 microM GTP gamma S. GDP beta S did not have any effect. Addition of protein kinase A catalytic subunit increased the ICa, probably through a phosphorylation process, but did not modify the charge movement. This suggests that protein kinase A and GTP gamma S are acting on different sites of the channel. It can be speculated that G-proteins may have a regulatory role in the excitation-contraction coupling mechanism by a direct effect on charge movement.

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Pertussis toxin pretreatment abolishes dihydropyridine inhibition of calcium flux in the 235-1 pituitary cell line

Cited by 10 publications

References 24 publications

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

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

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

Charge movement and calcium currents in skeletal muscle fibers are enhanced by GTP?S

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