LAUSR

Abstract Prostanoid EP receptor agonists are used for a number of clinical indications but may be associated with gastric disturbance. In the present studies we used the ferret and sulprostone (30 &mgr;g/kg, i.p.) to investigate the role of EP3/1 receptors in mechanisms of emesis and defaecation. The emetic response was antagonized significantly by (+)‐(2 S,3 S)−3‐(2‐methoxybenzylamino)−2‐phenlypiperidine hydrochloride (CP‐99,994; 10 mg/kg, i.p.; P<0.05), but not by metoclopramide (0.3 and 3 mg/kg), ondansetron (0.1 and 1 mg/kg), or scopolamine (3 mg/kg); promethazine (3 mg/kg) potentiated emesis by approximately 82% (P<0.05). Out of the drugs tested, only scopolamine (3 mg/kg) reduced significantly the defaecatory and/or tenesmus response (P<0.05). Bilateral abdominal vagotomy was ineffective to reduce sulprostone (30 &mgr;g/kg, i.p.)‐induced emesis and defaection and/or tenesmus. However, sulprostone (10 &mgr;g, i.c.v.) administered into the fourth ventricle was emetic but did not induce defaection or tenesmus. These data suggests that the action of sulprostone to induce emesis and defaecation and/or tenesmus is largely independent of the abdominal vagal system, with emesis involving central mechanisms. Emetic mechanisms appear dissociated from those mediating defaecation and/or tenesmus.