AJP - Gastrointestinal and Liver Physiology, Vol 269, Issue 6 940-G944, Copyright © 1995 by American Physiological Society
Effect on muscarinic acetylcholine receptors after experimental neuronal ablation in rat colon
T. Inoue, T. Okasora and E. Okamoto
Department of Surgery, Hyogo College of Medicine, Japan.
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 with a control group
undergoing a sham operation. The treated group showed that the decreased
number of ganglion cells of the myenteric plexus on routine stain and
acetylcholinesterase staining demonstrated the myenteric plexus in the
treated group diminished acetylcholinesterase 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 x 10(-8) in
treated muscle and 2.2 x 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 in untreated animals
(228 +/- 26.1 and 135 +/- 42.9 fmol/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 acetylcholine receptors.
