TY - JOUR
T1 - Long-term effects of extrinsic denervation on VIP and substance P innervation in circular muscle of rat jejunum
AU - Kasparek, Michael S.
AU - Fatima, Javairiah
AU - Iqbal, Corey W.
AU - Duenes, Judith A.
AU - Sarr, Michael G.
N1 - Funding Information:
Acknowledgment We want to thank Deborah I. Frank for her expert assistance in the preparation of this manuscript. This study was supported by grant DK 39337 from the National Institutes of Health, United States Public Health Services (M.G.S.) and grant KA 2329/1-1 from the Deutsche Forschungsgemeinschaft, Germany (M.S.K.).
PY - 2007/10
Y1 - 2007/10
N2 - 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.
AB - 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.
KW - Extrinsic denervation
KW - Motility
KW - Small intestine
KW - Substance P
KW - Vasoactive intestinal polypeptide
UR - http://www.scopus.com/inward/record.url?scp=34548585978&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548585978&partnerID=8YFLogxK
U2 - 10.1007/s11605-007-0212-1
DO - 10.1007/s11605-007-0212-1
M3 - Article
C2 - 17634766
AN - SCOPUS:34548585978
SN - 1091-255X
VL - 11
SP - 1339
EP - 1350
JO - Journal of Gastrointestinal Surgery
JF - Journal of Gastrointestinal Surgery
IS - 10
ER -