Lysophosphatidylcholine activates extracellular-signal-regulated protein kinase and potentiates vascular contractile responses in rat aorta.
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.
Suenaga
Hiroshi
H
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Japan.
Kamata
Katsuo
K
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D008244:Lysophosphatidylcholines; D020928:Mitogen-Activated Protein Kinases; D011188:Potassium