Abstract
Prostaglandin E2 (PGE2) exerts its biological effects through 4 different receptor subtypes, EP-1, EP-2,
EP-3, and EP-4. Recently we have demonstrated the importance of the prostaglandin
E2 receptor subtype EP-2 in the healing of bone defects and fractures. This discovery
led to the identification of CP-533,536, an EP-2 selective agonist, a promising therapeutic
alternative for the enhancement of bone healing and the treatment of fractures (J
Bone Miner Res 18 (2003) 2033).
PGE2 has a myriad of effects throughout the body including the induction of uterine contractions,
which results in termination of pregnancies. Our objective in this study was to determine
the role of the EP-2 receptor and specifically that of CP-533,536, an EP-2 specific
agonist, to induce uterine contractions and terminate pregnancy in guinea pigs, an
animal model of human pregnancy. Preliminary experiments confirmed earlier reports
that the guinea pig uterus was more sensitive than that of the rat. The guinea pig
uterus contains the four PGE2 receptor subtypes, and ex vivo treatment of the uterus with PGE2 as expected causes profound uterine contractions. However, using receptor selective
prostaglandin agonists including CP-533,536 we showed that the EP-1 and 3 receptors
not the EP-2 receptor is responsible for the induction of uterine contractions of
PGE2. Further, CP-533,536 did not antagonize the ability of PGE2 to induce uterine contractions in this model.
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Article info
Publication history
Published online: October 11, 2004
Accepted:
August 26,
2004
Received:
June 10,
2004
Identification
Copyright
© 2004 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
