Y2 receptors mediate an inhibition of intestinal motility in the mouse

Sarah Forbes1, Herbert Herzog2, Helen Cox1. 1Kings College London, London, United Kingdom, 2Garvan Institute of Medical Research, Sydney, Australia.

Exposure to acute stress alters gastrointestinal transit, typically inducing an inhibition of gastric emptying and acceleration of colonic motility via a central neuropeptide Y (NPY) pathway in rodents. Previous studies have indicated its analogue, peptide YY (PYY), delays ileal and colonic motility to optimise digestive processes and induce satiety through peripheral Y2 receptors. It is possible NPY, in addition to PYY, provides endogenous protection against stress-induced motility and diarrhoea in the periphery through tonic activation of Y2 receptors on vagal and enteric neurons. We tested this hypothesis by monitoring small intestinal transit (SIT) in vivo and colonic motility in vitro. SIT was determined 30 minutes after intra-gastric administration of a charcoal marker (10% plant charcoal in 5% gum acacia) in WT, NPY-/- and PYY-/- mice (male and female with mixed 129/SvJ/ C57BL/6 background, body weight 28.8 ± 0.9g, aged 21 ± 1 week) under basal or restrained conditions (30 minutes), and in WT mice treated with the Y2 antagonist BIIE0246 (60μg/100μl i.p.). The rate of colonic faecal pellet propulsion was measured in vitro over 20 minutes in all genotypes and in the presence and absence of BIIE0246 (1μM) in WT mice. PYY-/- mice demonstrated significantly faster SIT than all other genotypes with and without restraint stress (P = 0.01, n = 4-6), whilst BIIE0246-treated WT mice displayed a significant increase in transit, but only after restraint stress (P<0.05, n = 4-6). The rate of colonic motility did not change between the genotypes, however BIIE0246-treated WT tissue had significantly accelerated faecal pellet propulsion (P<0.05, n = 4-6). This data confirms the Y2 receptor is involved in the inhibition of SIT which is largely mediated by PYY and this mechanism is amplified under acute stressed conditions. It further suggests the tonic activation of intramural Y2 receptors by either endogenous peptide provides protection against changes in colonic motility.

Tache et al. (2001). Am J Physiol, 280,173-177.

Funded by the BBSRC.