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.