Effects of substance P on human colonic mucosa in vitro

Am J Physiol. 1999 Jun;276(6):G1473-83. doi: 10.1152/ajpgi.1999.276.6.G1473.


Previous studies indicated that the peptide substance P (SP) causes Cl--dependent secretion in animal colonic mucosa. We investigated the effects of SP in human colonic mucosa mounted in Ussing chamber. Drugs for pharmacological characterization of SP-induced responses were applied 30 min before SP. Serosal, but not luminal, administration of SP (10(-8) to 10(-6) M) induced a rapid, monophasic concentration and Cl--dependent, bumetanide-sensitive short-circuit current (Isc) increase, which was inhibited by the SP neurokinin 1 (NK1)-receptor antagonist CP-96345, the neuronal blocker TTX, the mast cell stabilizer lodoxamide, the histamine 1-receptor antagonist pyrilamine, and the PG synthesis inhibitor indomethacin. SP caused TTX- and lodoxamide-sensitive histamine release from colonic mucosa. Two-photon microscopy revealed NK1 (SP)-receptor immunoreactivity on nerve cells. The tyrosine kinase inhibitor genistein concentration dependently blocked SP-induced Isc increase without impairing forskolin- and carbachol-mediated Isc increase. We conclude that SP stimulates Cl--dependent secretion in human colon by a pathway(s) involving mucosal nerves, mast cells, and the mast cell product histamine. Our results also indicate that tyrosine kinases may be involved in this SP-induced response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Colon / cytology
  • Colon / drug effects*
  • Colon / metabolism
  • Colon / physiology
  • Electric Impedance
  • Electrophysiology
  • Genistein / pharmacology
  • Histamine / physiology
  • Histamine Release / physiology
  • Humans
  • In Vitro Techniques
  • Indomethacin / pharmacology
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / physiology
  • Ions
  • Mast Cells / physiology
  • Receptors, Neurokinin-1 / metabolism
  • Substance P / pharmacology*
  • Tetrodotoxin / pharmacology
  • Tissue Distribution / physiology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Ions
  • Receptors, Neurokinin-1
  • Substance P
  • Tetrodotoxin
  • Histamine
  • Genistein
  • Indomethacin