A role of peptidergic nerves in the internal anal sphincter of Hirschsprung's disease.
BACKGROUND
It is not clear what contribution the internal anal sphincter makes to the impaired motility observed in patients with Hirschsprung's disease (HD). Neuropeptides have recently been shown to be neurotransmitters in the nonadrenergic, noncholinergic inhibitory and excitatory nerves in the human gut. To clarify the physiologic significance of vasoactive intestinal polypeptide and substance P in the internal anal sphincter of HD (aganglionosis), we investigated the enteric nerve responses on lesional and normal internal anal sphincter muscle strips above the dentate line.


METHODS
The lesional and normal internal anal sphincter muscle strips above the dentate line were derived from patient with HD (9 cases) and patients who underwent rectal amputation for low rectal cancers (8 cases). A mechanographic technique was used to evaluate in vitro muscle responses to these peptides of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers.


RESULTS
Nonadrenergic, noncholinergic inhibitory nerves were found to act on the normal internal anal sphincter but had no effect on the enteric nerves in aganglionosis. Peptidergic (vasoactive intestinal polypeptide and substance P) nerves were found to act on normal colon, but no effect was observed in the aganglionic internal anal sphincter.


CONCLUSIONS
These findings suggest that peptidergic nerves play an important role in the impaired motility observed in the internal anal sphincter with HD.
Tomita
R
R
First Department of Surgery, Nihon University School of Medicine, Tokyo, Japan.
Morita
K
K
Tanjoh
K
K
Munakata
K
K
D000368:Aged; D001003:Anal Canal / Q000294:innervation* / Q000502:physiology / Q000503:physiopathology*; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005725:Ganglia, Autonomic / Q000502:physiology / Q000503:physiopathology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D006627:Hirschsprung Disease / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology / Q000503:physiopathology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012004:Rectal Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D013373:Substance P / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D010643:Phenoxybenzamine; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D001285:Atropine; D011433:Propranolol