Substance p as a mediator of colonic secretory reflexes.
Cooke, Helen J., M. Sidhu, Paula Fox, Y. Z. Wang, D. and Ellen M.
Zimmermann.
Dept. Physiology, The Ohio State University, Columbus, OH 43210,
and the Division of Gastroenterology, Dept. Internal Medicine,
University of Michigan, Ann Arbor, MI 48109
APStracts 3:0186G, 1996.
The role of substance P in neural reflex pathways activated by
stroking was investigated in muscle-stripped segments of distal colon
from guinea pigs. Stroking the mucosal surface with a brush at 1/s
evoked an increase in short-circuit current (Isc) indicative of
chloride secretion. The response to mucosal stroking was maximally
reduced by 69-75% by the antagonist, GR82334. The agonist,
[Sar9,Met(O2)11] substance P, caused a bumetanide-sensitive increase
in Isc when added to the mucosal or serosal bath. Ablation of
extrinsic afferents with acute or chronic administration of capsaicin
did not alter the mucosal stroking response. Reverse transcription
-polymerase chain reaction and in situ hybridization revealed the
presence of NK1 receptor messenger RNA in isolated colonocytes or
crypt glands. Ligand binding of 125I-Bolton-Hunter substance P was
inhibited by GR82334 with an IC50 of 0.84 nM. The results demonstrate
a role for substance P released from capsaicin-insensitive submucosal
neurons and in mucosal stroking reflexes. The presence of NK1
receptors on isolated colonocytes suggests that appropriate elements
are present for axon reflex activation of intestinal epithelial
cells.
Received 19 January 1996; accepted in final form 13 September
1996.
APS Manuscript Number G31-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996