Role of VIP and Substance P in NANC Innervation in the Longitudinal Smooth Muscle of the Rat Jejunum—Influence of Extrinsic Denervation

Kasparek, Michael S.; Fatima, Javairiah; Iqbal, Corey W.; Duenes, Judith A.; Sarr, Michael G.

doi:10.1016/j.jss.2007.01.021

« Previous Next »Journal of Surgical Research
Volume 141, Issue 1 , Pages 22-30, July 2007

Role of VIP and Substance P in NANC Innervation in the Longitudinal Smooth Muscle of the Rat Jejunum—Influence of Extrinsic Denervation1

Michael S. Kasparek, M.D.
- Department of Surgery and Gastrointestinal Research Unit, Mayo Clinic, Rochester, Minnesota
- Department of General Surgery, Eberhard Karls University, Tuebingen, Germany
Javairiah Fatima, M.D.
- Department of Surgery and Gastrointestinal Research Unit, Mayo Clinic, Rochester, Minnesota
Corey W. Iqbal, M.D.
- Department of Surgery and Gastrointestinal Research Unit, Mayo Clinic, Rochester, Minnesota
Judith A. Duenes, B.A.
- Department of Surgery and Gastrointestinal Research Unit, Mayo Clinic, Rochester, Minnesota
Michael G. Sarr, M.D.
- Department of Surgery and Gastrointestinal Research Unit, Mayo Clinic, Rochester, Minnesota
- To whom correspondence and reprint requests should be addressed at Department of Surgery and Gastrointestinal Research Unit, Mayo Clinic, 200 First Street SW, Rochester, MN, 55902.

Received 8 January 2007 published online 21 May 2007.

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 ≥ 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-Phe⁶, Leu¹⁷]-VIP) increased contractile activity in NC, but not in TA-8 and SBT-8. The Substance P antagonist ([D-Pro², 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.

Key Words: Vasoactive Intestinal Polypeptide, Substance P, motility, small intestine, extrinsic innervation, small intestinal transplantation, enteric nervous system, nonadrenergic noncholinergic innervation

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1 Parts of this work were presented at the Joint International Society Meeting in Neurogastroenterology and GI Motility in Boston, MA, September, 2006; at the 2nd Academic Surgical Congress in Phoenix, AZ, February, 2007; at the Annual Meeting of the German Surgical Society, Munich, Germany, May, 2007; and was published in Abstract form (Neurogastroenterol Motil 18:779, 2006 and Chirurgisches Forum 2007 [German]).

PII: S0022-4804(07)00030-3

doi:10.1016/j.jss.2007.01.021

« Previous Next »Journal of Surgical Research
Volume 141, Issue 1 , Pages 22-30, July 2007

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