Long-term effects of extrinsic denervation on VIP and substance P innervation in circular muscle of rat jejunum

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

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Intestinal denervation contributes to enteric motor dysfunction after small bowel transplantation (SBT). Our aim was to determine long-term effects of extrinsic denervation on function of nonadrenergic, noncholinergic innervation with substance P and vasoactive intestinal polypeptide (VIP). Contractile activity of jejunal circular muscle strips from six age-matched, naive control rats (NC) and eight rats 1 year after syngeneic SBT was studied in tissue chambers. Spontaneous contractile activity did not differ between groups. Exogenous VIP inhibited contractile activity dose-dependently to a comparable degree in both groups. The VIP antagonist ([d-p-Cl-Phe6,Leu 17]-VIP) and the nitric oxide synthase inhibitor l-N G-nitro-arginine did not affect VIP-induced inhibition but increased contractile activity during electrical field stimulation (EFS) in both groups. Exogenous substance P increased contractile activity dose-dependently, greater in NC than SBT. The substance P antagonist ([d-Pro2,d-Trp 7,9]-substance P) inhibited effects of exogenous substance P and decreased the excitatory EFS response. Immunohistofluorescence showed tyrosine hydroxylase staining after SBT indicating sympathetic reinnervation. In jejunal circular muscle after chronic denervation, response to exogenous substance P, but not VIP, is decreased, whereas endogenous release of both neurotransmitters is preserved. Alterations in balance of excitatory and inhibitory pathways occur despite extrinsic reinnervation and might contribute to enteric motor dysfunction after SBT.

Original languageEnglish (US)
Pages (from-to)1339-1350
Number of pages12
JournalJournal of Gastrointestinal Surgery
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2007

Keywords

  • Extrinsic denervation
  • Motility
  • Small intestine
  • Substance P
  • Vasoactive intestinal polypeptide

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

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