DIFFERENTIAL RESPONSES TO PROSTAGLANDINS IN THE CIRCULAR AND LONGITUDINAL MUSCLE LAYERS OF THE MURINE ILEUM.

Abstract

Prostaglandin E₂ (PGE₂) actions on intestinal motility are complex due the differential expression of the PGE₂ receptors EP1-EP4. We sought to determine the actions of PGE₂ 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 PGE₂ receptor activation on circular and longitudinal muscle layers. In the two muscle layers PGE₂ produced differential responses. In the circular muscle layer PGE₂ caused dose-dependent membrane hyperpolarization and 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 TTX and L-NNA, but inhibited by the K_ATP channel antagonist, glibenclamide. The actions of PGE₂ on the circular muscle layer were mimicked by the selective EP₂ and EP₄ agonists ONO AE1-259 and ONO AE1-329, respectively. The actions of PGE₂ were partially inhibited by the EP4 antagonist ONO AE3-208. The EP₁ agonist ONO DI-004 produced little effect while the EP3 agonist ONO AE-248 caused dose-dependent membrane depolarization. In comparison, PGE₂ produced increased tone and phasic contractions in the longitudinal muscle layer that was mimicked by ONO DI-004 and ONO AE-248, while EP₂ and EP₄ agonists had little effect on contractile activity. These data suggest that differential expression of PGE₂ receptors on intestinal muscle layers can produce antagonistic actions on intestinal motility.