Dose-response effects of indomethacin and PGE₂ on electromechanical activity of in vivo rabbit ileum

We determined dose-response characteristics of indomethacin and prostaglandin E₂ on the myoelectric activity in ileum of anesthetized New Zealand White rabbits. Monopolar electrodes and an intraluminal saline-filled catheter were used to simultaneously record electrical and mechanical activity. Thirty minutes after injection of 3.0, 5.0, and 10.0 mg/kg indomethacin, the percentage of slow waves with action potentials increased significantly from 10% to over 80%; at 60 min action potential activity decreased but remained dose dependent and significantly greater than controls. Action potential activity correlated with phasic increases in intraluminal pressure. Low-dose indomethacin (1.5 mg/kg) did not significantly alter action potential activity. Action potential activity induced by indomethacin (5 mg/kg) decreased dose dependently after infusion of prostaglandin E₂ (PGE₂, 1-28 μg/kg). In summary, dose-dependent action potential activity was induced by indomethacin and reversed by PGE₂. Endogenous inhibitory prostaglandins (PGE₂ or others) appear to modulate activity of specific excitatory neuromuscular circuits in in vivo ileum.