The aim of this study was to investigate the role of PGE₂ in LPS effects on ACh-induced contractions of rabbits intestinal segments in vitro with two different protocols.

In the first protocol, rabbits were treated with saline or LPS (0.2, 2 or 20 µg kg^-1) I.V. injected as a bolus. Rabbits were humanely killed by a blow on the head. Intestinal segments were removed 90 min after LPS administration. Pieces of duodenum, jejunum and ileum (10 mm X 5 mm) were vertically suspended in the direction of longitudinal muscle fibres, in a thermostatically controlled organ bath (10 ml capacity). The bath contained Tyrode solution at 37 °C to reach pH 7.4 and was gassed with 95 % O₂ and 5 % CO₂. Segments were stretched passively to an initial tension of 20 mN. Each segment was connected to an isometric transducer and mechanical activities were recorded, stored and analysed with a computer program. ACh non-cumulative concentration-response curves were constructed with and without LPS. In the second protocol, intestinal segments isolated from LPS non-treated rabbits were incubated with Ringer or LPS (0.03, 0.3, 3, and 30 µg ml^-1). ACh 10^-4 M contractions were recorded without LPS as the control. After, LPS was added to the bath and ACh contractions were compared with the control.

DE₅₀ values of ACh were 3.6 X 10^-7, 4.9 X 10^-7 and 5.1 X 10^-7 M in duodenum, jejunum and ileum, respectively. After LPS treatment (0.2 µg kg^-1), DE₅₀ was 2.6 X 10^-6, 1.0 X 10^-6 and 4.5 X 10^-7 M in duodenum, jejunum and ileum, respectively. When added to the bath, LPS also significantly reduced ACh-induced contractions (43 % reduction in duodenum, 35 % in jejunum and 17 % in ileum). Indomethacin (1 mg kg^-1) antagonised LPS effects when it was administered before LPS. PGE₂ (8 µg kg^-1, I.V.) reduced ACh-induced contractions and mimicked LPS actions.

The results show that LPS decreases ACh-induced contractions and that prostaglandins are involved in this action.

This work was supported by CICYT AGF97-0922 and DGI AGL2000-1228.