Phospholipase A(2) is involved in thapsigargin-induced sodium influx in human lymphocytes

Previously, we reported that emptying of intracellular Ca2+ pools with endo plasmatic Ca2+-ATP-ase inhibitor thapsigargin leads to the Na+ influx in hu man lymphocytes (M. Tepel et al., 1994, J, Biol, Chem, 269, 26239-26242). I n the present study we examined the mechanism underlying the thapsigargin-i nduced Na+ entry. We found that the thapsigarin-induced increase in Na+ con centration was effectively inhibited by three structurally unrelated phosph olipase A(2) (PLA(2)) inhibitors, p-bromophenacyl bromide, 3-(4-octadecyl)- benzoylacrylic acid (OBAA), and bromoenol lactone (BEL), The thapsigargin-i nduced Na+ influx could be mimicked by PLA(2) exogenously added to the lymp hocyte suspension. In addition, thapsigarsn stimulated formation of arachid onic acid (AA), the physiological PLA(2) product. AA induced Nai entry in a time- and concentration-dependent fashion. Both, thapsigargin-induced Nainflux and AA liberation were completely inhibited in the presence of tyros ine kinase inhibitor genistein but not in the absence of extracellular Ca2. Collectively, these data show that thapsigargin-induced Na+ entry is asso ciated with tyrosine kinase-dependent stimulation of PLA(2), (C) 2000 Acade mic Press.