AJP - Gastrointestinal and Liver Physiology, Vol 257, Issue 3 447-G453, Copyright © 1989 by American Physiological Society
Substance P: mechanism of action and receptor distribution at the feline ileocecal sphincter region
R. D. Rothstein, E. Johnson and A. Ouyang
Department of Medicine, University of Pennsylvania, Hospital of University of Pennsylvania, Philadelphia 19104.
The purpose of this study was to determine the mechanism of action of
substance P at the distal ileum, ileocecal sphincter (ICS), and proximal
colon in the cat and to determine the localization of substance P receptors
at these sites by autoradiography. Intraluminal pressures and myoelectric
activity were recorded at the feline distal ileum, ICS, and colon.
Substance P caused a tonic and phasic spike-dependent contractile response
at all three sites. The antagonists propranolol, phentolamine, and naloxone
did not affect the contractile response to substance P at the ileum, ICS,
or colon. The ganglionic blocker trimethaphan camsylate potentiated the
response to substance P at all three sites, P less than 0.05. Both atropine
and tetrodotoxin reduced the response of substance P at the ileal site. At
the ICS, atropine or tetrodotoxin reduced, but did not obliterate, the
effect of substance P. Neither atropine nor tetrodotoxin reduced substance
P-induced colonic contractions. By use of autoradiography, specific binding
for substance P was determined to be present at all three sites with the
greatest concentration of substance P receptors in the circular muscle
layer. In conclusion, these studies suggest multiple sites of action of
substance P. At the ileum, substance P causes contraction via a cholinergic
pathway. At the ICS, substance P has an excitatory action through a
cholinergic pathway and also at smooth muscle receptors. In the proximal
colon, the excitatory action of substance P is via smooth muscle receptors.
An inhibitory ganglionic pathway also exists at all three sites. Substance
P receptors exist predominantly in the circular muscle region of the ileum,
ICS, and the proximal colon.
