Abstract
Prostaglandin E(2) (PGE(2)) actions on intestinal motility are complex due to the differential expression of the PGE(2) receptors EP(1)-EP(4). We sought to determine the actions of PGE(2) on electrical pacemaker and contractile activity of the circular and longitudinal muscle layers of the murine small intestine. Intracellular microelectrode and isometric force measurements were performed to examine the effects of PGE(2) receptor activation on circular and longitudinal muscle layers. In the two muscle layers, PGE(2) produced differential responses. In the circular muscle layer, PGE(2) caused dose-dependent membrane hyperpolarization and a reduction in slow-wave amplitude, accompanied by a decrease in the amplitude of phasic contractions. Membrane hyperpolarization and the reduction in slow-wave amplitude and phasic contractions were insensitive to tetrodotoxin (TTX) and N(ω)-nitro-l-arginine (l-NNA) but inhibited by the K(ATP) channel antagonist glibenclamide. The actions of PGE(2) on the circular muscle layer were mimicked by the selective EP(2) and EP(4) agonists ONO AE1-259 and ONO AE1-329, respectively. The actions of PGE(2) were partially inhibited by the EP(4) antagonist ONO AE3-208. The EP(1) agonist ONO-DI-004 produced little effect, whereas the EP3 agonist ONO-AE-248 caused dose-dependent membrane depolarization. In comparison, PGE(2) produced increased tone and phasic contractions in the longitudinal muscle layer that was mimicked by ONO-DI-004 and ONO-AE-248, whereas EP(2) and EP(4) agonists had little effect on contractile activity. These data suggest that differential expression of PGE(2) receptors on intestinal muscle layers can produce antagonistic actions on intestinal motility.NEW & NOTEWORTHY Prostaglandins are lipid mediators that have complex actions on gastrointestinal motility that are highly dependent on the expression of the receptor subtypes where they exert their actions. PGE(2) has inhibitory or excitatory effects on circular or longitudinal muscle layers of the small intestine. Despite many studies of the effects of prostaglandins on tissue contractility, little is known about the specific receptors eliciting these effects. The present study examines functional receptor expression in the small intestine.