Effects of gestational age on prostaglandin EP receptor expression and functional involvement during in vitro contraction of the guinea pig uterus.
Prostaglandin E(2) (PGE(2)) exerts diverse biological effects through four G-protein-coupled cell surface receptor subtypes, EP1-4. This study's objective was to characterize EP1-4 receptor mRNA expression within pregnant guinea pig myometrium during early implantation stage (gestation day [GD] 6) and late stage gestation (GD 50) and evaluate in vitro contractile activity of receptor subtype selective agonists. Using RT-PCR, qualitative gene expression patterns of EP2, EP3, and EP4 mRNA were detected in the myometrium and remained unchanged between the gestational ages. EP1 mRNA remained undetected in pregnant tissue. In vitro contractile activity was evaluated in GD 6 and GD 50 myometrium using vehicle and EP agonists PGE(2), 17-phenyl trinor PGE(2), sulprostone, misoprostol, and CP-533,536. All spasmogens in pregnant myometrium were EP1/EP3 selective agonists, though likely acting via EP3 receptors in this test model. CP-533,536--a highly selective EP2 receptor agonist--and the vehicle failed to induce myometrial contraction at both gestational ages.
Terry
K K
KK
Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. ketti.k.kerry@pfizer.com
Lebel
W S
WS
Riccardi
K A
KA
Grasser
W A
WA
Thompson
D D
DD
Paralkar
V M
VM
D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D006168:Guinea Pigs; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D010120:Oxytocics / Q000494:pharmacology; D011247:Pregnancy; D011725:Pyridines / Q000494:pharmacology; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
C475539:CP533536; D010120:Oxytocics; D011725:Pyridines; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D015232:Dinoprostone