Role of E-type prostaglandin receptor EP3 in the vasoconstrictor activity evoked by prostacyclin in thromboxane-prostanoid receptor deficient mice.
Prostacyclin, also termed as prostaglandin I2(PGI2), 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 PGI2, 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 PGI2, were isolated for functional and biochemical analyses. Here, we showed that the contractile response evoked by PGI2was 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 PGI2in such vessels of TP-/-mice. These results suggest that EP3 along with TP contributes to vasoconstrictor responses evoked by PGI2, and hence imply a novel mechanism for endothelial cyclooxygenase metabolites (which consist mainly of PGI2) in regulating vascular functions.
Dept of Pathology, The 2nd Affiliated Hospital, Shantou University Medical College, Shantou, China.
Zhenhua
Z
Li
Cardiovascular Research Center, Shantou University Medical College, Shantou, China.
Yingzhan
Y
Zhang
Cardiovascular Research Center, Shantou University Medical College, Shantou, China.
Bin
B
Liu
The Central Lab, Shantou University Medical College, Shantou, China.
Wenhong
W
Luo
The Central Lab, Shantou University Medical College, Shantou, China.
Hui
H
Li
Cardiovascular Research Center, Shantou University Medical College, Shantou, China.
Yingbi
Y
Zhou
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000235:genetics* / Q000378:metabolism; D017482:Receptors, Thromboxane / Q000172:deficiency / Q000235:genetics*; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology*
C545648:Ptger3 protein, mouse; D058308:Receptors, Prostaglandin E, EP3 Subtype; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; D011464:Epoprostenol; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2