Back
Acta Physiologica 2006; Volume 187, Supplement 659
The Scandinavian Physiological Society's Annual Meeting
8/11/2006-8/13/2006
Reykjavik, Iceland
PROSTAGLANDIN E2 MEDIATES VASORELAXATION THROUGH EP4-RECEPTOR MEDIATED SYNTHESIS OF NO
Abstract number: P32
NIELSEN1 SS, HRISTOVSKA1 AM, RASMUSSEN1 LE, HANSEN1 PBL, NUSING2 R, SKOTT1 O, JENSEN1 BL
1University of Southern Denmark, Medical Biology, 21 Winslowparken, Odense C, Denmark
2Johan Wolfgang Goethe-University, Frankfurt/Main, Germany [email protected]
PGE2 induces vasodilatation in various vascular beds through activation of EP2 or EP4 receptors. EP4 receptor activation can stimulate the PI-3 kinase and protein kinase B/Akt and increase endothelial NO-synthase (eNOS) activity through phosphorylation of Ser1179. Thus it was hypothesized that PGE2 induces vasorelaxation through EP4 receptor-mediated stimulation of the eNOS. A Myograph System (610 M, Danish Myo Technology) was used to measure isometric force in mouse aorta segments. PGE2 evoked a concentration-dependent relaxation (EC50(-log M) = 7,2) of phenylephrine-contracted (3x10-7 M) segments, which was abolished by the NO-synthase inhibitor NG-Nitro-L-Arginine Methyl Ester (L-NAME) (10-4 M) as well as by the guanylate cyclase inhibitor ODQ (10-6 M). The PGE2 mediated relaxation was absent in segments without endothelium as in segments from eNOS-/- and EP4 -/- mice. EP4 receptor expression was confirmed in aorta by reverse transcription polymerase chain reaction (RT-PCR). In a second series, segments treated with PGE2 were immediately frozen in liquid nitrogen and used for western blotting (anti-phospho-eNOS-Ser1177, anti-phospho-eNOS-Thr495 and anti-eNOS) and measurements of cGMP concentrations (EIA cGMP kit, Cayman Chemical). Western blotting showed dephosphorylation of eNOS at Thr495 and unchanged or less phosphorylation of Ser1177. The cGMP content was increased in segments treated with PGE2. In conclusion, PGE2 evokes an endothelial EP4 receptor-mediated, NO-dependent, relaxation of mouse aorta. It is proposed that PGE2 evokes a dephosphorylation of the eNOS-Thr495 residue while changes in phosphorylation at Ser1179 appear less important.
To cite this abstract, please use the following information:
Acta Physiologica 2006; Volume 187, Supplement 659 :P32