Role of prostanoid EP3/1 receptors in mechanisms of emesis and defaecation in ferrets

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 mu 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 mu g/kg, i.p.)-induced emesis and defaection and/or tenesmus. However, sulprostone (10 mu 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.