Prostaglandin E2 receptor EP4-selective antagonist inhibits lipopolysaccharide-induced cervical ripening in rabbits.
BACKGROUND
The purpose of this study was to examine whether EP4 as prostaglandin (PG) E2 receptor is involved in lipopolysaccharide (LPS)-induced cervical ripening.


METHODS
New Zealand White non-pregnant rabbits were randomly allocated to 4 equal groups and treated with vaginal suppositories containing LPS with various concentrations of EP4-selective antagonist once daily for 3 days, and then sacrificed for analysis. Analysis was performed in order to examine the inhibitory effect of EP4 antagonist on LPS-induced cervical ripening. The expression of EP4 in a cervix treated with LPS was examined immunohistochemically. The percent of cervical extensibility in the segment of cervix as the tensile strength was determined with 5.8 g of constant perpendicular stretching. The ripening area of the cervix with edematous changes in H&E sections was calculated by a microscopic system with a computer-assisted digital analyser. Type-1 collagenase activity was determined in cervical tissue using FITC-labelled type-1 collagen.


RESULTS
Immunohistochemical study shows the positive staining of EP4 at the interstitial cells in the cervix treated with LPS. The extensibility, cervical edematous area and type-1 collagenase activity are significantly reduced in the cervix treated with LPS in the presence of EP4 antagonist compared with that treated with LPS alone.


CONCLUSIONS
These data implicates the EP4 as the PGE2 receptor involved in LPS-induced cervical ripening.
Fukuda
Yuka
Y
Department of Obstetrics & Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Sugimura
Motoi
M
Suzuki
Kazunao
K
Kanayama
Naohiro
N
D000818:Animals; D020070:Cervical Ripening / Q000187:drug effects* / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D023421:Models, Animal; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology*; D010654:Phenylbutyrates / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D011817:Rabbits; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors* / Q000502:physiology; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013488:Suppositories
C487890:4-(4-cyano-2-(2-(4-fluoronaphthalen-1-yl)propionylamino)phenyl)butyric acid; D008070:Lipopolysaccharides; D009281:Naphthalenes; D010654:Phenylbutyrates; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013488:Suppositories; D017364:Collagenases; C417249:collagenase 1