STIMULATION OF GASTROINTESTINAL MOTILITY BY CISPLATIN IN THE FERRET - ACTIVATION OF AN INTRINSIC CHOLINERGIC MECHANISM DISSOCIATED FROM EMESIS

Motility was recorded from the corpus, antrum and small intestine of the urethane anaesthetised ferret. The gastrointestinal effects of the highly emetic cytotoxic anticancer agent, cisplatin were investigated following intravenous administration (I 0 mg/kg i. v.). Following injection, cisplatin induced a prompt onset (< 2 min) increase in motility (tone and contraction amplitude) in all regions with a duration of < 15 min. Acute vagotomy did not abolish the effect but reduced the peak amplitude in the antrum only. Chronic subdiaphragmatic vagotomy significantly enhanced the cisplatin-induced rise in tone in the corpus, the contraction amplitude in the antrum and the duration of the response in the duodenum. The stimulatory effect of cisplatin was blocked in all regions by atropine but not naloxone or the 5-HT3 receptor antagonist ondansetron. This study reports a previously undescribed gastrointestinal motility effect of cisplatin in vivo that is temporally dissociated from emesis. It is proposed that the results provide evidence for a neuroactive effect of cisplatin on enteric cholinergic neurones.