Lysophosphatidylcholine activates extracellular-signal-regulated protein kinase and potentiates vascular contractile responses in rat aorta.
نویسندگان
چکیده
We previously reported that in the endothelium-denuded rat aorta, lysophosphatidylcholine (LPC) potentiates the contractile responses induced by high-K(+), UK14,304 (a selective alpha(2)-adrenoceptor agonist), and phorbol ester with an associated tyrosine-phosphorylation of proteins. To further investigate this phenomenon, we examined the effects of extracellular-signal-regulated protein kinase (ERK)-kinase (MEK) inhibitors on the LPC-induced potentiation of the contractile responses to high-K(+) and UK14,304 in this tissue. Although PD98059 (3 x 10(-)(5) M) did not affect the high-K(+)-induced contractile response itself, it selectively inhibited the potentiating effect of LPC on the contraction and strongly inhibited the LPC-induced augmentation of the associated increase in [Ca(2+)](i). PD98059 also attenuated the LPC-induced augmentations of the increases in [Ca(2+)](i) and contractile tension induced by UK14,304. U0126 (5 x 10(-)(5) M), another MEK inhibitor, also attenuated the potentiating effect of LPC on high-K(+)-induced contractions. Western blot analysis revealed that LPC produced an increase in ERK-phosphorylation, and that this was inhibited by PD98059. Nicardipine inhibited the contractile response to 15 mM K(+) in the LPC-treated aorta, but not the increase in ERK-phosphorylation induced by LPC. These results suggest that the LPC-induced augmentation of contractile responses in the rat aorta is due to activation of ERK, which in turn regulates Ca(2+) influx.
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ورودعنوان ژورنال:
- Journal of pharmacological sciences
دوره 92 4 شماره
صفحات -
تاریخ انتشار 2003