Intracellular signaling by 8-epi-prostaglandin F2 alpha is mediated by thromboxane A2/prostaglandin endoperoxide receptors in porcine carotid arteries.
Intracellular signaling by 8-epi-prostaglandin F2 alpha is mediated by thromboxane A2/prostaglandin endoperoxide receptors in porcine carotid arteries.
复制标题
8-表观前列腺素 F2 α 的细胞内信号传导由猪颈动脉中的血栓素 A2/前列腺素内过氧化物受体介导。
DOI：
10.1006/bbrc.1996.1272
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发表时间：
1996
影响因子：
3.1
通讯作者：
Adam,LP
中科院分区：
文献类型：
--
作者：
Mohler,ER;Franklin,MT;Adam,LP
为探讨8-表-前列腺素F2α（8-epi-PGF 2 α）增加血管张力的细胞内信号转导机制，我们检测了8-epi-PGF 2 α或PGF 2 α孵育的猪颈动脉中丝裂原活化蛋白激酶（MAPK）活性和肌球蛋白调节轻链（LC 20）磷酸化。在8-epi-PGF_（2 α）或PGF_（2 α）刺激下，MAPK活性和收缩力平行上升，并在激动剂作用期间（2 h）保持不变。LC 20磷酸化水平上升，然后部分下降与任一激动剂刺激期间。受体拮抗剂SQ-29548和BMS-180291可完全抑制8-epi-PGF 2 α对收缩、MAPK活性和肌球蛋白轻链磷酸化的作用;这些化合物仅部分抑制PGF 2 α的作用。因此，在完全分化的血管平滑肌中，8-epi-PGF 2 α的细胞内信号传导（导致MAPK活化和肌球蛋白磷酸化增加）是由血栓烷A2/前列腺素内过氧化物受体的活化特异性介导的。动脉粥样硬化等血管病理过程引起的脂质过氧化和8-epi-PGF 2 α的产生，导致平滑肌中两条细胞内信号通路的激活：一条通路导致MAPK的激活，而另一条通路导致肌球蛋白轻链磷酸化。
To investigate the mechanisms for intracellular signaling and increased vascular tone by 8-epi-prostaglandin F2α(8-epi-PGF2α), we measured mitogen-activated protein kinase (MAPK) activity and myosin regulatory light chain (LC20) phosphorylation in porcine carotid arteries incubated with 8-epi-PGF2αor PGF2α. With stimulation by either 8-epi-PGF2αor PGF2α, MAPK activity and the force of contraction rose in parallel and were maintained during the time of exposure to agonist (2 hours). LC20phosphorylation levels rose and then partially declined during stimulation with either agonist. The effects of 8-epi-PGF2αon contraction, MAPK activity, and myosin light chain phosphorylation were completely inhibited by the receptor antagonists, SQ-29548 and BMS-180291; the effects of PGF2αwere only partially inhibited by these compounds. Thus, intracellular signaling by 8-epi-PGF2αin fully differentiated vascular smooth muscle, resulting in MAPK activation and increased myosin phosphorylation, is specifically mediated by an activation of thromboxane A2/prostaglandin endoperoxide receptors. Lipid peroxidation and 8-epi-PGF2αproduction, resulting from such vascular pathological processes as atherosclerosis, lead to an activation of two intracellular signaling pathways in smooth muscle: one pathway results in the activation of MAPK, while the other results in myosin light chain phosphorylation.