PT  - JOURNAL ARTICLE
AU  - Fujino, Hiromichi
AU  - Regan, John W.
TI  - EP<sub>4</sub> Prostanoid Receptor Coupling to a Pertussis Toxin-Sensitive Inhibitory G Protein
AID  - 10.1124/mol.105.017749
DP  - 2006 Jan 01
TA  - Molecular Pharmacology
PG  - 5--10
VI  - 69
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/69/1/5.short
4100  - http://molpharm.aspetjournals.org/content/69/1/5.full
SO  - Mol Pharmacol2006 Jan 01; 69
AB  - The EP2 and EP4 prostanoid receptor subtypes are G-protein-coupled receptors for prostaglandin E2 (PGE2). Both receptor subtypes are known to couple to the stimulatory guanine nucleotide binding protein (Gαs) and, after stimulation with PGE2, can increase the formation of intracellular cAMP. In addition, PGE2 stimulation of the EP4 receptor can activate phosphatidylinositol 3-kinase (PI3K) leading to phosphorylation of the extracellular signal-regulated kinases (ERKs) and induction of early growth response factor-1 (EGR-1) (J Biol Chem 278: 12151–12156, 2003). We now report that the PGE2-mediated phosphorylation of the ERKs and induction of EGR-1 can be blocked by pretreatment of EP4-expressing cells with pertussis toxin (PTX). Furthermore, pretreatment with PTX increased the amount of PGE2-stimulated intracellular cAMP formation in EP4-expressing cells but not in EP2-expressing cells. These data indicate that the EP4 prostanoid receptor subtype, but not the EP2, couples to a PTX-sensitive inhibitory G-protein (Gαi) that can inhibit cAMP-dependent signaling and activate PI3K/ERK-dependent signaling.