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Updated: Jul 11, 2026
In vitro Functional Characterization of Mouse Colorectal Afferent Endings
Published on: January 21, 2015
Substance P causes a chloride-dependent short-circuit current response in rabbit colonic mucosa in vitro
M Riegler1, I Castagliuolo, M Wlk
1Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Background:
The neuropeptide substance P (SP) induces secretion in animals. The effect of SP on rabbit colon is not known. We therefore investigated the effect of SP on rabbit colonic mucosa mounted in Ussing chambers.
Methods:
Colonic mucosae were incubated with SP in Cl -containing or Cl -free buffer. Drugs for pharmacologic characterization of SP-induced electrophysiologic changes were applied to the serosal bath 30 min before SP administration.
Results:
Serosal, but not luminal, administration of SP (10(-8)-10(-6) M) induced a rapid, transient, bumetanide-sensitive, dose- and chloride-dependent short-circuit current (Isc) increase (P < 0.001), which was inhibited by 85%, 80%, 82%, 90%, and 70% after serosal preincubation with the neurokinin-1 (NK-1) receptor antagonist CP-96,345, the neuronal blocker tetrodotoxin (10(-6)M), the mast cell stabilizer lodoxamide (10(-6) M), the H1-receptor antagonist pyrilamine (10(-6) M), or the prostaglandin synthesis inhibitor indomethacin (10(-6) M), respectively (P < 0.001).
Conclusions:
SP stimulates a chloride-dependent Isc increase in the rabbit colon which is mediated by nerves and mast cells and the mast cell product histamine.
