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

•In the ileum of inflamed dogs vs. controls, the number of SP neurons was similar.•In the ileum, SP mucosal fibers resulted slightly decreased in inflamed vs. control dogs.•The number of ileal neurons expressing NK1R was similar in inflamed vs. controls.•In inflamed dogs, muscle cells and immune cells strongly expressed NK1R.•Gut inflammation seems to be associated with tachykininergic changes in dogs.

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.