Changes in peptidergic neurotransmission during postoperative ileus in rat circular jejunal muscle

Abstract

Our aim was to explore unknown changes in neurotransmission with vasoactive intestinal peptide (VIP) and Substance P (Sub P) during postoperative ileus (POI). Contractile activity of rat circular jejunal muscle strips was studied in five groups (n = 6/group): Naïve controls, sham controls 12 h and 3 days after laparotomy, and rats 12 h, 3 days after induction of POI. Dose-responses to VIP (10(-10) -10(-7) M), Sub P (3 × 10(-10) -3 × 10(-7) M), and electrical field stimulation (EFS, to study endogenous release of neurotransmitters) were studied with different antagonists. Intestinal transit, inflammatory cells and immunoreactivity for VIP and Sub P were investigated in the bowel wall and cellular Finkel osteo sarcoma expression was determined in vagal afferent and efferent nuclei of the brainstem. Postoperative ileus characterized by delayed intestinal transit and intramural inflammation was associated with an increased inhibitory effect of VIP on contractile activity. A biphasic impact was observed for Sub P with a decrease in its excitatory potential on contractility at 12 h, followed by a later increase 3 days postoperatively. Inhibitory response to EFS was increased, whereas the excitatory response decreased in ileus animals. VIP expression was increased in all postoperative animals while only animals 3 days after ileus induction showed increased Sub P expression in the myenteric plexus. These changes were associated with an activation of afferent but not efferent vagal nuclei in the brain stem. Specific, time-dependent changes in peptidergic neurotransmission with VIP and Sub P occur during POI that are associated with vagal afferent activation, but are independent of the activation of efferent vagal pathways.