Previous studies have failed to reveal an effect of the gastrointestinal peptide hormone ghrelin on colonic motility. In the present work, ghrelin was applied into the lumbo-sacral spinal cord in the region of defecation control centres, and a synthetic ghrelin receptor agonist, CP464709, which crosses the blood-brain barrier, was applied intravenously or into the lumbo-sacral cord. Both ghrelin and CP464709 elicited propulsive contractions and emptying of the colon in anaesthetized rats. In conscious rats, subcutaneous CP464709 caused fecal expulsion. The sites of action and nerve pathways involved in the stimulation of the colon by ghrelin receptor activation were investigated in anaesthetized rats. Intrathecal application of CP464709 at L6-S1, but not application at ponto-medullary levels or to the thoracic spinal cord, elicited propulsive contractions. The stimulation evoked by intravenous CP464709 was prevented if the pelvic nerve outflows were severed, but not if the spinal cord was cut rostral to the defecation centre at L6-S3. The response was also blocked by hexamethonium. When ghrelin, applied intrathecally, was used to desensitize its receptors, the effect of intravenous CP464709 was blocked. CP464709 did not affect small intestine motility or the amplitudes of visceromotor reflexes caused by colorectal distension. It is concluded that activation of ghrelin receptors in the lumbo-sacral spinal cord triggers co-ordinated propulsive contractions that empty the colo-rectum. The pathways through which these responses are generated pass out of the spinal cord via the pelvic nerves and cause propulsive contractions through activation of enteric neurons.

We have used spatio-temporal maps derived from video images to investigate propagated contractions of the rat small intestine in vivo. The abdomen, including an exteriorized segment of jejunum, was housed in a humid chamber with a viewing window. Video records were converted to spatio-temporal maps of jejunal diameter changes. Intraluminal pressure and fluid outflow were measured. Contractions occupied 3.8 +/- 0.2 cm of intestine and propagated anally at 3.1 +/- 0.2 mm s(-1) when baseline pressure was 4 mmHg. Contractions at any one point lasted 8.7 +/- 0.6 s. Contractions often occurred in clusters; within cluster frequencies were 2.28 +/- 0.04 min(-1). Pressure waves, with amplitudes greater than about 9 mmHg, expelled fluid when the baseline pressure was 4 mmHg. In the presence of L-NAME, circular muscle contractions occurred at a high frequency, but they were not propagated. We conclude that video recording methods give good spatio-temporal resolution of intestinal movement when applied in vivo. They reveal neurally-mediated propulsive contractions, similar to those previously recorded from intestinal segments in vitro. The propagated contractions had speeds of propagation that were slower and frequencies of occurrence that were less than speeds and frequencies of slow waves in the rat small intestine.

Colchicine may be a cause of neuropathy. An experimental model to study this is developed.

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