Substance P and the neurokinin-1 receptor expression in dog ileum with and without inflammation

In the gastrointestinal tract, the tachykinin Substance P (SP) is involved in motility, fluid and electrolyte secretion, and blood flow and regulation of immunoinflammatory response. SP exerts its biological activity on target cells by interacting mainly with the neurokinin-1 receptor (NK₁R). The present study aims to quantify the percentage of SP-immunoreactive (SP-IR) enteric neurons and the density of SP-IR nerve fibers in the ileum of control dogs (CTRL-dogs; n=7) vs dogs with spontaneous ileal inflammation (INF-dogs; n=8). In addition, the percentage of enteric neurons bearing NK₁R, and nitrergic neurons (nNOS-IR) expressing NK₁R immunoreactivity were evaluated in both groups. The percentages of SP-IR neurons were similar in CTRL- and INF-dogs, in either the myenteric (MP) (15±8% vs. 16±7%, respectively) and submucosal plexus (SMP) (26±7% vs. 24±14%, respectively). In INF-dogs, the density of SP-IR mucosal nerve fibers showed a trend to decrease (P=0.07). Myenteric neurons of CTRL- and INF-dogs expressed similar percentages of NK₁R-immunoreactivity (39±5% vs. 38±20%, respectively). Submucosal NK₁R-IR neurons were occasionally observed in a CTRL-dog. MP nitrergic neurons bearing NK₁R showed a trend to decrease in INF-dogs vs. CTRL- dogs (41±22% vs. 65±10%, respectively; P=0.11). In INF-dogs, muscle cells and immune cells overexpressed NK₁R immunoreactivity. These findings should be taken as a warning for possible intestinal motility disorders, which might occur during administration of NK₁R-antagonist drugs. Conversely, the strong expression of NK₁R immunoreactivity observed in muscle and mucosal immune cells of inflamed tissues may provide a rationale for the use of NK₁R antagonist drugs in the treatment of intestinal inflammation.