The effects of neurotensin in the colon of patients with slow transit constipation

BACKGROUND/AIMS: The cause of dysmotility in the colon of patients with slow transit constipation (STC) is still unknown. Neurotensin (NT) has recently been shown to be a neurotransmitter in the non-adrenergic non-cholinergic (NANC) excitatory nerves of the human alimentary tract. To clarify the physiological significance of NT in the colon of patients with STC, we examined the enteric nerve responses in lesional and normal bowel segments derived from patients with STC and patients who underwent colon resection for colonic cancers. METHODOLOGY: Twenty-eight preparations were taken from colonic lesions in 10 patients with slow transit constipation (2 men and 8 women, aged 23 to 70 years, mean 46.3 years). Forty-six preparations were taken from the normal colons of 16 patients with colonic cancer (8 men and 8 women, aged 40 to 66 years, mean 50.1 years). A mechanographic technique was used to evaluate in vitro muscle responses to electrical field stimulation (EFS) before and after treatment with various autonomic nerve blockers and NT. RESULTS: After blocking both the adrenergic and cholinergic nerves (Experiment 1), NT showed contraction reaction on both normal and STC colons in a concentration-dependent manner. The contraction reactions to NT in the normal colon were more dominant than those in the STC colon. There were significant differences between the frequency of contraction reactions to NT in normal colon strips and those in STC colon strips (P < 0.001). Following addition of tetrodotoxin (Experiment II), all muscle strips of normal and STC colons demonstrated contraction responses by NT. The effects of NT in the normal and STC colon muscle strips were essentially the same as in experiment 1, although the extent of contraction was somewhat diminished. CONCLUSIONS: Those results suggested that NT acts both via NANC excitatory nerves and also directly on the colonic smooth muscle. A decrease of NT mediates NANC excitatory nerves and plays an important role in the dysmotility observed in the colons of patients with STC.