CART-peptide immunoreactivity in enteric nerves in patients with Hirschsprung's disease.
OBJECTIVE
Cocaine- and amphetamine-regulated transcript (CART)-peptide is found in the brain and participates in the control of feeding behavior. It is also expressed in the peripheral nervous system and is suggested to have neuromodulatory and/or neurotrophic effects in rat intestine. The aims of this study were to investigate the presence of CART-peptide in the normal ganglionic as well as aganglionic intestine from patients with Hirschsprung's disease and the peptide's possible coexistence with other neurotransmitters.


METHODS
Intestinal specimens from nine patients with Hirschsprung's disease were examined using immunohistochemistry. A double immunostaining technique was used in order to elucidate the presence of CART-peptide in NOS and VIP-containing enteric neurons.


RESULTS
In ganglionic intestine, CART-peptide was found in numerous nerve fibers, predominantly within the smooth muscle layers and in myenteric nerve cell bodies. A high degree of co-localization of CART with NOS and VIP was seen. Only very few CART immunoreactive nerve fibers and no nerve cell bodies were found in the aganglionic intestine.


CONCLUSIONS
This is the first report on the presence of CART-peptide in the human intestine. In the ganglionic intestine CART was detected mainly in myenteric neurons, while only very few CART-IR nerve fibers were found in the aganglionic intestine. This, together with the coexistence of CART with NOS and VIP, indicates an intrinsic origin of the CART-containing neurons and suggests that CART may influence NO and VIP-induced effects.
Gunnarsdóttir
A
A
Department of Pediatric Surgery, Lund University Hospital, Lund, Sweden. Anna.Gunnarsdottir@med.lu.se
Wierup
N
N
Larsson
L T
LT
Kuhar
M J
MJ
Ekblad
E
E
D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D015415:Biomarkers / Q000378:metabolism; D002675:Child, Preschool; D003106:Colon / Q000294:innervation*; D017615:Enteric Nervous System / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006627:Hirschsprung Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D009130:Muscle, Smooth / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D018377:Neurotransmitter Agents; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D000888:Antibodies, Anti-Idiotypic; D015415:Biomarkers; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D014660:Vasoactive Intestinal Peptide; D019001:Nitric Oxide Synthase