Role of E-type prostaglandin receptor EP3 in the vasoconstrictor activity evoked by prostacyclin in thromboxane-prostanoid receptor deficient mice

Abstract Prostacyclin, also termed as prostaglandin I 2 (PGI 2 ), evokes contraction in vessels with limited expression of the prostacyclin receptor. Although the thromboxane-prostanoid receptor (TP) is proposed to mediate such a response of PGI 2 , other unknown receptor(s) might also be involved. TP knockout (TP −/− ) mice were thus designed and used to test the hypothesis. Vessels, which normally show contraction to PGI 2 , were isolated for functional and biochemical analyses. Here, we showed that the contractile response evoked by PGI 2 was indeed only partially abolished in the abdominal aorta of TP −/− mice. Interestingly, further antagonizing the E-type prostaglandin receptor EP3 removed the remaining contractile activity, resulting in relaxation evoked by PGI 2 in such vessels of TP −/− mice. These results suggest that EP3 along with TP contributes to vasoconstrictor responses evoked by PGI 2 , and hence imply a novel mechanism for endothelial cyclooxygenase metabolites (which consist mainly of PGI 2 ) in regulating vascular functions.