Mechanisms of activated Ca2+ entry in the rat pancreatoma cell line, AR4-2J
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Mechanisms of activated Ca2+ entry in the rat pancreatoma cell line, AR4-2J. / Bird, G S; Takemura, H; Thastrup, Ole; Putney, J W; Menniti, F S.
In: Cell Calcium, Vol. 13, No. 1, 1992, p. 49-58.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Mechanisms of activated Ca2+ entry in the rat pancreatoma cell line, AR4-2J
AU - Bird, G S
AU - Takemura, H
AU - Thastrup, Ole
AU - Putney, J W
AU - Menniti, F S
PY - 1992
Y1 - 1992
N2 - The characteristics of Ca2+ entry activated by surface receptor agonists and membrane depolarization were studied in the rat pancreatoma cell line, AR4-2J. Ca2+ mobilization activated by substance P, bombesin, or muscarinic receptor stimulation was found to involve both Ca2+ release and entry. In addition, depolarization of the surface membrane of AR4-2J cells with elevated concentrations of K+ activated Ca2+ entry. Ca2+ entry induced by membrane depolarization was inhibited by the L-channel antagonist, nimodipine, while that due to surface receptor agonists was not inhibited by this agent. The microsomal Ca(2+)-ATPase inhibitor, thapsigargin, caused both depletion of the agonist-sensitive intracellular Ca2+ pool and sustained Ca2+ influx indistinguishable from that produced by bombesin or methacholine. These results confirm that, unlike the pancreatic acinar cells from which they are presumably derived, AR4-2J cells express voltage-sensitive, dihydropyridine-inhibitable Ca2+ channels. However, in contrast to previous reports with this cell line, in the AR4-2J cells in use in our laboratory, and under our experimental conditions, surface receptor agonists (including substance P) do not cause Ca2+ influx through voltage-sensitive Ca2+ channels. Instead, we conclude that agonist-activated Ca2+ mobilization is initiated by (1,4,5)IP3-mediated intracellular Ca2+ release and that Ca2+ influx is regulated primarily, if not exclusively, by the state of depletion of the (1,4,5)IP3-sensitive intracellular Ca2+ pool.
AB - The characteristics of Ca2+ entry activated by surface receptor agonists and membrane depolarization were studied in the rat pancreatoma cell line, AR4-2J. Ca2+ mobilization activated by substance P, bombesin, or muscarinic receptor stimulation was found to involve both Ca2+ release and entry. In addition, depolarization of the surface membrane of AR4-2J cells with elevated concentrations of K+ activated Ca2+ entry. Ca2+ entry induced by membrane depolarization was inhibited by the L-channel antagonist, nimodipine, while that due to surface receptor agonists was not inhibited by this agent. The microsomal Ca(2+)-ATPase inhibitor, thapsigargin, caused both depletion of the agonist-sensitive intracellular Ca2+ pool and sustained Ca2+ influx indistinguishable from that produced by bombesin or methacholine. These results confirm that, unlike the pancreatic acinar cells from which they are presumably derived, AR4-2J cells express voltage-sensitive, dihydropyridine-inhibitable Ca2+ channels. However, in contrast to previous reports with this cell line, in the AR4-2J cells in use in our laboratory, and under our experimental conditions, surface receptor agonists (including substance P) do not cause Ca2+ influx through voltage-sensitive Ca2+ channels. Instead, we conclude that agonist-activated Ca2+ mobilization is initiated by (1,4,5)IP3-mediated intracellular Ca2+ release and that Ca2+ influx is regulated primarily, if not exclusively, by the state of depletion of the (1,4,5)IP3-sensitive intracellular Ca2+ pool.
KW - Animals
KW - Bombesin
KW - Calcium
KW - Calcium Channels
KW - Calcium-Transporting ATPases
KW - Fura-2
KW - Inositol 1,4,5-Trisphosphate
KW - Methacholine Chloride
KW - Nimodipine
KW - Rats
KW - Signal Transduction
KW - Substance P
KW - Terpenes
KW - Thapsigargin
KW - Tumor Cells, Cultured
M3 - Journal article
C2 - 1371721
VL - 13
SP - 49
EP - 58
JO - Cell Calcium
JF - Cell Calcium
SN - 0143-4160
IS - 1
ER -
ID: 43349542