Substance P causes a chloride-dependent short-circuit current response in rabbit colonic mucosa in vitro.
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.
Riegler
M
M
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Castagliuolo
I
I
Wlk
M
M
Pothoulakis
C
C
D000818:Animals; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008407:Mast Cells; D064729:Neurokinin-1 Receptor Antagonists; D011453:Prostaglandins / Q000502:physiology; D011817:Rabbits; D013373:Substance P / Q000494:pharmacology*
D018118:Chloride Channels; D002712:Chlorides; D064729:Neurokinin-1 Receptor Antagonists; D011453:Prostaglandins; D013373:Substance P