Regulation of the peptidergic nerves (substance P and vasoactive intestinal peptide) in the colon of women patients with slow transit constipation: an in vitro study.

BACKGROUND/AIMS In histological studies, there is evidence to suggest a diminution of the peptidergic nerves such as vasoactive intestinal peptide (VIP) and substance P (SP) in the enteric nervous system in the colon of patients with slow transit constipation (STC). To clarify the pathophysiological significance of peptidergic nerves in the colon of patients with STC, we investigated the enteric nerve responses on pathological and normal bowel segments derived from patients with STC and patients who underwent colon resection for colon cancers, respectively. METHODOLOGY Twenty-eight preparations were taken from the pathological sigmoid colon of 16 women with STC (aged 40-58 years, average 48.8 years). Forty-eight preparations were taken from the normal sigmoid colon of 20 women with colonic cancer (aged 40-55 years, average 49.6 years). A mechanographic technique was used to evaluate in vitro muscle responses to VIP and SP of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. RESULTS Responses mediated by non-adrenergic non-cholinergic (NANC) inhibitory nerves were found in the normal colon, but were more frequently in the colon with STC than in the normal colon (p < 0.01). Responses mediated by excitatory nerves such as cholinergic nerves were more dominant in the normal colon than in the STC colon. At 1 x 10(-8), 1 x 10(-7), 1 x 10(-6) g/mL, VIP and SP in both the normal and STC colonic muscle strips produced a concentration-dependent relaxation to VIP and contraction to SP. In addition, the relaxation reaction to VIP in the colon with STC was also weaker than in the normal colon (p < 0.01). The contraction reaction to SP in the colon with STC was weaker than in the normal colon (p < 0.01). VIP acts through neural mechanisms, whereas SP may act both through nerves and also directly on both the normal and STC muscle strips. CONCLUSIONS Responses mediated by NANC inhibitory nerves were significantly increased in the colon with STC compared with the normal colon. A decrease of responses to peptidergic nerves such as SP and VIP may also play an important role in the impaired motility observed in the colon of patients with STC. These results indicate that the disturbances in the neural component of the enteric nervous system in the colon of women patients with STC may initiate or contribute to the functional changes.