Intracellular signaling by 8-epi-prostaglandin F(2α) is mediated by thromboxane A2/prostaglandin endoperoxide receptors in porcine carotid arteries

Abstract

To investigate the mechanisms for intracellular signaling and increased vascular tone by 8-epi-prostaglandin F(2α) (8-epi-PGF(2α)), we measured mitogen-activated protein kinase (MAPK) activity and myosin regulatory light chain (LC20) phosphorylation in porcine carotid arteries incubated with 8-epi-PGF(2α) or PGF(2α). With stimulation by either 8-epi-PGF(2α) or PGF(2α), MAPK activity and the force of contraction rose in parallel and were maintained during the time of exposure to agonist (2 hours). LC20 phosphorylation levels rose and then partially declined during stimulation with either agonist. The effects of 8-epi-PGF(2α) on contraction, MAPK activity, and myosin light chain phosphorylation were completely inhibited by the receptor antagonists, SQ-29548 and BMS-180291; the effects of PGF(2α) were only partially inhibited by these compounds. Thus, intracellular signaling by 8-epi-PGF(2α) in 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-PGF(2α) production, 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.