INTRACELLULAR SIGNALING BY 8-EPI-PROSTAGLANDIN F2-ALPHA IS MEDIATED BY THROMBOXANE A(2) PROSTAGLANDIN ENDOPEROXIDE RECEPTORS IN PORCINE CAROTID ARTERIES/

To investigate the mechanisms for intracellular signaling and increase d vascular tone by 8-epi-prostaglandin F-2 alpha (8-epi-PGF(2 alpha)), we measured mitogen-activated protein kinase (MAPK) activity and myos in regulatory light chain (LC(20)) phosphorylation in porcine carotid arteries incubated with 8-epi-PGF(2 alpha) or PGF(2 alpha). With stimu lation by either 8-epi-PGF(2 alpha) or PGF(2 alpha), MAPK activity and the force of contraction rose in parallel and were maintained during the time of exposure to agonist (2 hours). LC(20) phosphorylation leve ls rose and then partially declined during stimulation with either ago nist. The effects of 8-epi-PGF(2 alpha) on contraction, MAPK activity, and myosin light chain phosphorylation were completely inhibited by t he receptor antagonists, SQ-29548 and BMS-180291; the effects of PGF(2 alpha) were only partially inhibited by these compounds. Thus, intrac ellular signaling by 8-epi-PGF(2 alpha) in fully differentiated vascul ar smooth muscle, resulting in MAPK activation and increased myosin ph osphorylation, is specifically mediated by an activation of thromboxan e A(2)/prostaglandin endoperoxide receptors. Lipid peroxidation and 8- epi-PGF(2 alpha) production, resulting from such vascular pathological processes as atherosclerosis, lead to an activation of two intracellu lar signaling pathways in smooth muscle: one pathway results in the ac tivation of MAPK, while the other results in myosin light chain phosph orylation. (C) 1996 Academic Press, Inc.