Substance P regulates migration in rat intestinal epithelial cells

Objective: The current study examined the effect of substance P (SP) upon intestinal epithelial cells and the mechanistic details of this interaction. Summary Background Data: Intestinal epithelial cells must be capable of migration to reseal mucosal wounds for several vital intestinal functions. This process is incompletely understood; however, recent evidence implicates the neurotransmitter SP in this process. Methods: Normal rat intestinal epithelial cells (IEC-6 cells) were studied to identify the presence of the SP receptor (NK-1 subtype) and then exposed to physiologic doses of SP and antagonists to assess for increased migration. Results: Examination IEC-6 cells revealed the presence of the SP receptor. Wounding of these cells followed by subsequent exposure to SP (10(-9) mol/L) resulted in increased migration. Similarly, SP-induced increases in intracellular calcium concentration and actomyosin stress fiber formation. These effects were all blocked through specific NK-1 receptor antagonists. Conclusions: These results indicate that SP stimulates intestinal epithelial migration and increases in calcium concentration. These data support a beneficial role for SP in the maintenance of intestinal mucosal homeostasis.