TY - JOUR

T1 - Cell Shrinkage is Essential in Lysophosphatidic Acid Signaling in Ehrlich Ascites

AU - Pedersen, Susanne

AU - Hoffmann, Else Kay

AU - Hougaard, Charlotte

AU - Lambert, Ian H.

PY - 2000

Y1 - 2000

N2 - The present study aimed at elucidating the initial intracellular lysophosphatidic acid (LPA)-induced signaling events, in order to investigate the sequence in which LPA affects the intracellular concentration of free, cytosolic Ca(2+), [Ca(2+)](i), ion channels, the F-actin cytoskeleton, cell volume and the Na(+)/H(+) exchanger. We found that stimulation of Ehrlich cells with LPA induced a transient, concentration-dependent increase in [Ca(2+)](i), which is due to Ca(2+) release from intracellular Ins(1,4,5)P(3)-sensitive stores as well as an influx of Ca(2+). The EC(50) values for LPA-induced Ca(2+) mobilization were estimated at 0.03 nm and 0.4 nm LPA in the presence and absence of extracellular Ca(2+), respectively. The LPA-induced increase in [Ca(2+)](i) resulted in (i) co-activation of Ca(2+)-activated, charybdotoxin (ChTX)-sensitive K(+) and niflumic acid-sensitive Cl(-) currents; (ii) a subsequent cell shrinkage and increased polymerization of F-actin, and (iii) activation of a Na(+)/H(+) exchange, resulting in a concentration-dependent intracellular alkalinization. The EC(50) value for the LPA-induced rate of alkalinization was estimated at 0. 37 nm LPA. When cell shrinkage was prevented, the LPA-induced activation of the Na(+)/H(+) exchanger was impaired. In conclusion, the initial signaling events induced by LPA involves activation of volume regulatory mechanisms.

AB - The present study aimed at elucidating the initial intracellular lysophosphatidic acid (LPA)-induced signaling events, in order to investigate the sequence in which LPA affects the intracellular concentration of free, cytosolic Ca(2+), [Ca(2+)](i), ion channels, the F-actin cytoskeleton, cell volume and the Na(+)/H(+) exchanger. We found that stimulation of Ehrlich cells with LPA induced a transient, concentration-dependent increase in [Ca(2+)](i), which is due to Ca(2+) release from intracellular Ins(1,4,5)P(3)-sensitive stores as well as an influx of Ca(2+). The EC(50) values for LPA-induced Ca(2+) mobilization were estimated at 0.03 nm and 0.4 nm LPA in the presence and absence of extracellular Ca(2+), respectively. The LPA-induced increase in [Ca(2+)](i) resulted in (i) co-activation of Ca(2+)-activated, charybdotoxin (ChTX)-sensitive K(+) and niflumic acid-sensitive Cl(-) currents; (ii) a subsequent cell shrinkage and increased polymerization of F-actin, and (iii) activation of a Na(+)/H(+) exchange, resulting in a concentration-dependent intracellular alkalinization. The EC(50) value for the LPA-induced rate of alkalinization was estimated at 0. 37 nm LPA. When cell shrinkage was prevented, the LPA-induced activation of the Na(+)/H(+) exchanger was impaired. In conclusion, the initial signaling events induced by LPA involves activation of volume regulatory mechanisms.

M3 - Journal article

VL - 173

SP - 19

EP - 29

JO - Journal of Membrane Biology

JF - Journal of Membrane Biology

SN - 0022-2631

IS - 1

ER -