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

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Abstract
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 micrograms/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.