Substance p induces ion secretion in mouse small intestine through effects on both enteric nerves and mast cells. Wang, Lu, Andrzej M. Stanisz, Barry K. Wershil, Stephen J. Galli, and Mary H. Perdue. Intestinal Diseases Research Programme, McMaster University, Hamilton, Ontario, Canada, and the Combined Program in Pediatric Gastroenterology and Nutrition, and Departments of Pathology, Beth Israel Hospital and Harvard Medical School, Boston, MA.
APStracts 2:0040G, 1995.
We used genetically mast cell-deficient WBB6F1-W/Wv (W/Wv) mice and congenic WBB6F1-+/+ normal (+/+) mice to examine the role of mast cells in substance P-induced intestinal ion secretion. Isolated sheets prepared from segments of mid-small intestine were studied in Ussing chambers. Substance P caused a dose-dependent increase in short-circuit current (Isc) that was 50% less in intestine from W/Wv compared with +/+ mice. Similar results were obtained for substance P4-11 (the C-terminus) and substance P methyl ester (a selective NK1 agonist). Histamine H1 or H2 antagonists, reduced the Isc responses to substance P in intestine from +/+ mice, but had no effect in that from W/Wv mice. In addition, reconstitution of intestinal mast cells in W/Wv mice by intravenous injection of +/+ bone marrow cells normalized the tissues' secretory responses to substance P or substance P methyl ester. However, in both W/Wv and +/+ mice, the selective NK1 antagonist, CP96,345, virtually abolished intestinal responses to substance P, and the responses were also markedly inhibited by neural blockade with tetrodotoxin (TTX). In contrast, in TTX pre-treated intestine, histamine antagonism caused a further reduction in the responses to substance P only in +/+ mouse tissues. Taken together, our results suggest that the effects of substance P on intestinal Isc responses are largely due to binding of the C -terminus to NK1 receptors, but that the neuropeptide acts via effects on both enteric nerves and mast cells. The data thus support the concept that both mast cells and enteric nerves participate in the regulation of substance P-induced intestinal ion secretion. 

Received 27 June 1994; accepted in final form 22 February 1995.
APS Manuscript Number G246-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.