Roles of prostaglandin E₂-EP1 receptor signaling in regulation of gastric motor activity and emptying

Abstract

Majima M. Roles of prostaglandin E 2-EP1 receptor signaling in regulation of gastric motor activity and emptying. Am J Physiol Gastrointest Liver Physiol 299: G1078 -G1086, 2010. First published August 26, 2010 doi:10.1152/ajpgi.00524.2009.-It is widely accepted that the inhibition of gastric motor activity as well as the maintenance of gastric mucosal blood flow and mucous secretion are important for the homeostasis of the gastric mucosa. The present study was performed to ascertain whether or not endogenous PGs, which can protect the stomach from noxious stimuli, affect gastric motor activity and emptying. The myoelectrical activity of rat gastric smooth muscle was increased at intragastric pressures of over 2 cmH 2O. Replacement of intragastric physiological saline with 1 M NaCl solution significantly increased PGI 2 and PGE2 in stomach and suppressed the myoelectrical activity under a pressure of 2 cmH 2O by 70%. Indomethacin inhibited the suppression of myoelectrical activity by 1 M NaCl. The myoelectrical activity under a pressure of 2 cmH 2O was suppressed by continuous infusion of a selective EP1 agonist (ONO-DI-004, 3-100 nmol·kg Ϫ1 ·min Ϫ1 ) into the gastric artery in a dose-dependent manner, but not by that of the PGI receptor agonist beraprost sodium (100 nmol·kg Ϫ1 ·min Ϫ1 ). Suppression of myoelectrical activity with 1 M NaCl was inhibited by continuous infusion of a selective EP1 antagonist (ONO-8711, 100 nmol·kg Ϫ1 ·min Ϫ1 ) into the gastric artery. Furthermore, gastric emptying was tested in EP1 knockout mice and their wild-type counterparts. Gastric emptying was strongly suppressed with intragastric 1 M NaCl in wild-type mice, but this 1 M NaCl-induced suppression was not seen in EP1 knockout mice. These results suggest that PGE 2-EP1 signaling has crucial roles in suppression of myoelectrical activity of gastric smooth muscles and inhibition of gastric emptying and that EP1 is an obvious target for drugs that control gastric emptying. myoelectrical activity; gastric emptying; hyperosmolarity

Lipopolysaccharide reduces food passage rate from the crop by a prostaglandin-independent mechanism in chickens

“…For example, it is reported that PGE2 contributes to suppression of gastric emptying induced by intragastric injection of a hyperosmolar NaCl solution in rats (Nishiyama et al ., 1992; Mizuguchi et al ., 2010). Intragastric injection of enprostil, a PGE2 derivative, also reduces gastric emptying of barium grains in rats (Sakurai et al ., 1996).…”

Possible mechanism for the gastro-intestinal adverse effects upon topical application of Prostaglandin F2α analogs

“…The stimulation of EP receptors could still reduce IOP [18,19], but might induce gastro-intestinal effects. EP1 signaling has crucial roles in the suppression of myoelectrical activity of gastric smooth muscles and inhibition of gastric emptying, as well as induction of contractions in the small intestine [20]. The activation of EP1 receptor by latanoprost or travoprost, in the absence of FP receptor, might incur obvious gastro-intestinal adverse effects, including nausea and vomiting.…”

At last, a truly selective EP2 receptor antagonist

“…Further, using selective ligands we have recently shown that in human airways, PGE 2 relaxes smooth muscle tone via the EP 4 receptor (Buckley et al ., 2011). Indeed, there has recently been a plethora of publications describing the actions of PGE 2 (Narumiya, 2009; Esaki et al ., 2010; Mizuguchi et al ., 2010; Aoki et al ., 2011; Hosono et al ., 2011). , thanks mainly to the excellent tools developed by Ono Pharma and the genetically modified mice produced by Professor Narumiya.…”

“…Further, using selective ligands we have recently shown that in human airways, PGE2 relaxes smooth muscle tone via the EP4 receptor (Buckley et al, 2011). Indeed, there has recently been a plethora of publications describing the actions of PGE2 (Narumiya, 2009;Esaki et al, 2010;Mizuguchi et al, 2010;Aoki et al, 2011;Hosono et al, 2011)., thanks mainly to the excellent tools developed by Ono Pharma and the genetically modified mice produced by Professor Narumiya.Investigations of the role of the EP2 receptor in responses mediated by PGE2 have proved to be difficult due to the lack of a suitable EP2 receptor antagonist. A recent publication in the British Journal of Pharmacology by af Forselles et al (2011) describing in detail a new EP2 receptor antagonist would suggest that there is now a complete set of EP receptor ligands.…”