PGE₂ may interact with at least four cell surface receptors (EP1-EP4). Pharmacological studies suggest that PGE₂ contricts the smooth muscle through EP1 and EP3. In contrast, PGE₂ relaxes vascular and intestinal smooth muscle through EP2 and EP4. EP1 receptor is presumed to stimulate intracellular Ca²⁺ mobilisation. The EP3 receptor inhibits adenylate cyclase and reduces levels of cAMP (Narumiya et al. 1999).

The aim of this study was to examine the PGE₂ receptors in intestinal longitudinal segments from rabbits in vitro.

Rabbits were humanely killed by a blow on the head. Pieces of duodenum, jejunum and ileum (10 mm X 5 mm) were cut into longitudinal smooth muscle segments. The preparations were vertically suspended in a thermostatically controlled organ bath (10 ml capacity). The bath contained Krebs 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. Non-cumulative concentration-response curves to PGE₂ and PGE₂ agonists (10^-9-10^-5 M) were constructed in duodenum, jejunum and ileum. Also, non-cumulative concentration-response curves to PGE₂ were made in the presence of atropine (10^-6 M), guanethidine (10^-6 M), tetrodotoxin (10^-6 M), and hexamethonium (10^-5 M).

PGE₂-induced contractions were dose dependent in duodenum, jejunum and ileum. Atropine, guanethidine, tetrodotoxin and hexamethonium did not modify the effect of PGE₂. These results suggest that the PGE₂ action was myogenic. Misoprostol, sulprostone, 17-phenyl PGE₂ and 16,16-dimethyl PGE₂ caused contractions in duodenum, jejunum and ileum. However, butaprost did not alter spontaneous contractions. The PGE₂-induced contractions were blocked in Ca²⁺-free medium plus EGTA 0.5 mM. Verapamil 10^-7 M, a Ca²⁺ channel antagonist, and staurosporine 5 X 10^-7 M, a protein kinase C inhibitor, diminished the contractions of PGE₂ in small intestine.

PGE₂-induced contractions in rabbit small intestine appear to act directly on smooth muscle cells and EP1 receptors probably are implicated. Furthermore, voltage-dependent Ca²⁺ channels and protein kinase C mediate the responses.

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