Background: This study was designed to determine changes in nonadrenergic, noncholinergic (NANC) neurotransmission mediated by Vasoactive Intestinal Polypeptide (VIP) and Substance P after small bowel transplantation (SBT).
Materials And Methods: Six groups of rats (n > or = 6 per group) were studied: naïve controls (NC); 1 wk after anesthesia/sham celiotomy (SC-1); 1 or 8 wk after jejunal and ileal transection/reanastomosis (TA-1, TA-8), or syngeneic, orthotopic SBT (SBT-1, SBT-8). Jejunal longitudinal muscle strips were studied under NANC-conditions for spontaneous contractile activity, response to exogenous VIP and Substance P, and electrical field stimulation (EFS).
Results: Spontaneous activity did not differ between the six groups. VIP inhibited contractile activity in all groups 1 wk postoperatively (P < 0.05), which was prevented by the NO synthase inhibitor L-N(G)-nitro arginine (L-NNA). In contrast, VIP had no effect in the other groups. Precontraction with Substance P exposed an inhibitory effect of VIP in all groups (P < 0.05 each). Substance P increased contractile activity in all groups, but to a lesser extent in SBT-8 compared with NC, TA-8, and SBT-1 (P < 0.05). The inhibitory effect of EFS at 6 Hz was prevented by L-NNA in NC and TA-8; addition of the VIP antagonist ([D-p-Cl-Phe(6), Leu(17)]-VIP) increased contractile activity in NC, but not in TA-8 and SBT-8. The Substance P antagonist ([D-Pro(2), D-Trp(7,9)]-Substance P) decreased contractile activity during EFS at 50 Hz in NC and SBT-8.
Conclusions: SBT decreased response to exogenous Substance P, although release of endogenous Substance P (EFS) is preserved. Changes in VIP signaling are acute and reversible and not caused by effects of SBT.
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