Effect of chronic, extrinsic denervation on functional NANC innervation with vasoactive intestinal polypeptide and substance P in longitudinal muscle of rat jejunum.
Intestinal denervation contributes to enteric motor dysfunction after intestinal transplantation [small bowel transplantation (SBT)]. Our aim was to determine long-term effects of extrinsic denervation on functional non-adrenergic, non-cholinergic innervation with vasoactive intestinal polypeptide (VIP) and substance P. Contractile activity of jejunal longitudinal muscle from six age-matched, naïve control rats (NC) and eight rats 1 year after syngeneic SBT were studied in tissue chambers. Spontaneous contractile activity did not differ between groups. Exogenous VIP inhibited contractile activity dose-dependently in both groups, greater in NC than in SBT. The VIP antagonist ([D-p-Cl-Phe(6),Leu(17)]-VIP) and the nitric oxide synthase inhibitor l-N(G)-nitro arginine prevented inhibition by exogenous VIP and electrical field stimulation (EFS) in both groups. Exogenous substance P increased contractile activity dose-dependently, greater in NC than in SBT. The substance P antagonist ([D-Pro(2),D-Trp(7,9)]-substance P) inhibited effects of exogenous substance P and increased the EFS-induced inhibitory response. Immunohistofluorescence showed staining for tyrosine hydroxylase in the jejunoileum 1 year after SBT suggesting sympathetic reinnervation. In rat jejunal longitudinal muscle after chronic denervation, response to exogenous VIP and substance P is decreased, while endogenous release of both neurotransmitters is preserved. These alterations in excitatory and inhibitory pathways occur despite extrinsic reinnervation and might contribute to enteric motor dysfunction after SBT.
Kasparek
M S
MS
Department of Surgery and Gastrointestinal Research Unit, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.
Fatima
J
J
Iqbal
C W
CW
Duenes
J A
JA
Sarr
M G
MG
D000375:Aging / Q000502:physiology; D000818:Animals; D003627:Data Interpretation, Statistical; D003714:Denervation; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000502:physiology*; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000637:transplantation; D007583:Jejunum / Q000294:innervation* / Q000502:physiology*; D008297:Male; D008856:Microscopy, Fluorescence; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D013373:Substance P / Q000037:antagonists & inhibitors / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000502:physiology*
D018377:Neurotransmitter Agents; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D014446:Tyrosine 3-Monooxygenase