Physiological studies on neurotensin in rat small bowel isografts

Background/Aims: The cause of dysmotility in the small intestine of patients with small bowel transplantation (SBT) is still unknown. It is established that neurotensin (NT) is released by stimulation of non-adrenergic non-cholinergic (NANC) excitatory nerves. It is considered that the ileum is more important than the jejunum in regard to digestive functions. In order to evaluate the intestinal function of rat ileal isografts, this study examined the enteric nerve responses to electrical field stimulation (EFS) and NT in the isografted rat ileum, using the normal ileum as a control. Methodology: Orthotopic entire small bowel transplantation (SBT) with portocaval drainage was performed from Lewis rats to Lewis rats. Grafted tissue specimens were obtained 130 days after SBT (n=8). As controls, normal segments of the ileum were obtained from untransplanted Lewis rats (n=20). A mechanograph was used to evaluate in vitro ileal responses to electrical field stimulation (EFS) of the adrenergic and cholinergic nerve before and after treatments with various autonomic nerve blockers and NT. Results: All ileal muscle strips used in the present studies responded to EFS before and after the blockade of both the adrenergic and cholinergic nerves. The intrinsic innervation contains both excitatory (cholinergic and NANC excitatory nerves) and inhibitory nerves (adrenergic and NANC inhibitory nerves) in the normal and isografted ileum of LEW rats. Excitatory nerves, especially NANC excitatory nerves, were more dominant in the isografted ileum than in the normal ileum (P<0.001). NANC inhibitory nerves were found to act on the normal ileum and to a greater extent in the isografted ileum (P<0.05). NT mediates the contraction reaction of NANC excitatory nerve in the normal ileum and to a greater extent in the isografted ileum (P<0.05). Conclusions: Contraction reactions of NT were observed in both the normal and isografted ileum, but were increased in the isografted ileum. The increase of the NT in mediating NANC excitatory nerves and decrease of the NANC inhibitory nerves may be largely related to the peristaltic abnormalities seen in the isografted LEW rat ileum.