Influence of tachykinin NK₂ receptors on intestinal sensitivity and motility in newborn rats

Abstract 

The effect of tachykinin neurokinin NK₂ receptors activation on intestinal propulsion and colorectal sensitivity was studied in 7–15days old newborn rats.

In a first set of experiments investigating the intestinal transit, the selective NK₂ receptor agonist, [βAla⁸]NKA-(4-10) was used. It produced an increase of the small intestinal transit measured by charcoal test of 54%, that was inhibited in a dose-dependent manner by nepadutant ([N⁴-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-l-asparaginyl-l-aspartyl-l-tryptophyl-l-phenylalanyl-l-2,3-diaminopropionyl-l-leucyl]-C-4.2-N-3.5-lactam-C-1.6-N-2.1-lactam), a known selective NK₂ receptor antagonist, orally administered 2–48h before the challenge with the NK₂ receptor agonist. Nepadutant did not affect the basal intestinal propulsion and showed a good oral bioavailability and long duration of action.

In another set of experiments investigating visceral sensitivity, a fixed distension volume of a balloon inserted intrarectally in 14–15days old newborns rats produced abdominal contractions (AC) that were increased after colonic application of acetic acid (50μl, 0.5%). In this latter condition nepadutant, at 0.5 and 2.5mg/kg p.o., significantly reduced the resulting AC. In control rats, untreated with acetic acid, nepadutant did not affect AC evoked by colorectal distension.

These findings show for the first time two models to assess intestinal motility and visceral sensitivity in newborn rats and indicate nepadutant as a valuable tool to assess the role of NK₂ receptors in the intestinal propulsive and nociceptive activity in infants.

Keywords: Intestinal transit, Nepadutant, Newborn rats, Tachykinin NK₂ receptors, Visceral sensitivity