Neurotensin Changes Propulsive Activity into a Segmental Motor Pattern in the Rat Colon

BACKGROUND/AIMS: Neurotensin is a gut-brain peptide with both inhibitory and excitatory actions on the colonic musculature; our objective was to understand the implications of this for motor patterns occurring in the intact colon of the rat. METHODS: The effects of neurotensin with concentrations ranging from 0.1-100 nM were studied in the intact rat colon in vitro, by investigating spatio-temporal maps created from video recordings of colonic motility before and after neurotensin. RESULTS: Low concentration of neurotensin (0.1-1 nM) inhibited propagating long distance contractions and rhythmic propagating motor complexes; in its place a slow propagating rhythmic segmental motor pattern developed. The neurotensin receptor 1 antagonist SR-48692 prevented the development of the segmental motor pattern. Higher concentrations of neurotensin (10 nM and 100 nM) were capable of restoring long distance contraction activity and inhibiting the segmental activity. The slow propagating segmental contraction showed a rhythmic contraction—relaxation cycle at the slow wave frequency originating from the interstitial cells of Cajal associated with the myenteric plexus pacemaker. High concentrations given without prior additions of low concentrations did not evoke the segmental motor pattern. These actions occurred when neurotensin was given in the bath solution or intraluminally. The segmental motor pattern evoked by neurotensin was inhibited by the neural conduction blocker lidocaine. CONCLUSIONS: Neurotensin (0.1-1 nM) inhibits the dominant propulsive motor patterns of the colon and a distinct motor pattern of rhythmic slow propagating segmental contractions develops. This motor pattern has the hallmarks of haustral boundary contractions.

Interstitial cells of Cajal. Pathology, injury and repair

Interstitial cells of Cajal [ICC] are specialised cells located within the musculature of the gastrointestinal tract [GIT]. Although they form only 5% of the cells in the musculature of the GIT, they play a critical role in regulating smooth muscle function and GIT motility in coordination with the enteric nervous system. C-kit is a transmembrane glycoprotein that plays a critical role in ICC development and maturation. Physiological conditions such as ageing, as well as pathological conditions that have different disease processes, negatively affect ICC networks and function. Absent or disordered ICC networks can be associated with disorders in GIT motility. This review highlights the mechanism of ICC recovery from various types of injury which entails understanding the development of ICC and the factors affecting it. ICC transformation into malignant tumours [gastrointestinal stromal tumours] and their potential as contributors to therapeutic resistance is also discussed