ETHYLISOPROPYLAMILORIDE-SENSITIVE PH CONTROL MECHANISMS MODULATE VASCULAR SMOOTH-MUSCLE CELL-GROWTH
ETHYLISOPROPYLAMILORIDE-SENSITIVE PH CONTROL MECHANISMS MODULATE VASCULAR SMOOTH-MUSCLE CELL-GROWTH
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DOI：
10.1152/ajpcell.1991.260.3.c581
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发表时间：
1991-03-01
影响因子：
--
通讯作者：
GRINPUKEL, S
中科院分区：
文献类型：
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作者：
BOBIK, A;GROOMS, A;GRINPUKEL, S
The reported effects of alterations in Na-H exchange activity on mitogenesis are variable and appear dependent on the cell type examined. We examined the effects of reductions in ethylisopropylamiloride (EIPA)-sensitive pH-regulating mechanisms including Na-H exchange and alterations in intracellular pH (pH(i) on the growth characteristics of rat aortic smooth muscle cells (RASM) cultured in serum-containing bicarbonate-buffered medium. Exposure of RASM replicating in bicarbonate-containing medium to the Na-H exchange inhibitors EIPA, dimethylamiloride (DMA), or amiloride (A) attenuated their replication rate. The order of potency of the inhibitors (EIPA > DMA >> A) was similar to their documented effects on Na-H exchange activity and to their order of potency for inhibiting recovery from CO2-induced acidosis in these cells. Reductions in pH(i) induced by lowering extracellular pH also attenuated the incorporation of [H-3] thymidine into DNA, while increases in pH(i) were associated with an acceleration in the rate of incorporation of [H-3]thymidine into DNA. The effects of the Na-H exchange inhibitors on RASM replication were due to a reduction in the ability of the smooth muscle cells to enter the S phase of the mitotic cell cycle. This appeared predominantly the consequence of effects late within the G1 phase of the cell cycle. Concentrations of EIPA that markedly reduced the ability of RASM to enter S phase and to replicate also attenuated the increase in protein synthesis occurring 6-8 h after exposure to serum. The early (0-2 h) increases in protein synthesis that occurred when quiescent RASM were intially exposed to serum were unaffected despite an attenuated Na-H exchange activity and reduced pH(i) in these cells. Taken together our observations indicate that effects on EIPA-sensitive pH(i) mechanisms such as Na-H exchange can modulate RASM growth via effects on pH(i) even in the presence of bicarbonate-containing medium. The apparent lack of effect on the early increase in protein synthesis indicates that reductions in Na-H exchange activity and the associated fall in pH(i) in RASM have the capability to convert an essentially proliferative response to a growth factor to a hypertrophic response.
