Hypersensitivity in acquired aganglionosis in rat colon is due to
an increase in the number of muscarinic acetylcholine receptors.
Inoue, Teruo, Tatsuo Okasora, and Eizo Okamoto.
Department of Surgery,Hyogo College of Medicine, 1-1 Mukogawa
-cho,Nishinomiya,Hyogo 663,JAPAN
APStracts 2:0143G, 1995.
The etiology of denervation hypersensitivity was studied using a rat
model. Degeneration of the myenteric plexus was produced by direct
application of 0.1% benzalkonium chloride to the serosal surface of
the distal colon. Thirty days later, the treated group was compared
to a control group undergoing a sham operation. The treated group
showed decreased number of ganglion cells of the myenteric plexus on
routine and acetylcholine esterase staining demonstrated the
myenteric plexus in treated group diminished acetylcholine esterase
activity. Methacholine 1%, a muscarinic agonist, increased
intraluminal pressure in treated but not control rats. The dose
-response curve of colonic muscle strips to oxotremorine showed a
shift to the left, indicating greater sensitivity, in the treated
bowel, with a 50% effective dose (ED50) of 2.5[lambda]10-8 in treated
muscle and 2.2[lambda]10-7 in controls. Binding studies using [3H]
-quinuclidinyl benzilate ([3H]QNB) showed that the specific maximal
binding (Bmax) for [3H]QNB was greater in treated than untreated
animals (228+/-26.1 and 135+/-42.9 fmoles/mg protein,respectively;
p<0.01), even though the dissociation constants (KD) were the
same (0.398+/-0.083 and 0.406+/-0.065). These findings show that
acquired denervation hypersensitivity in this model is due to an
increase in the number of muscarinic acethylcholine receptors.
Received 14 November 1994; accepted in final form 14 June 1995.
APS Manuscript Number G448-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.