The effect of orexins on intestinal motility in vitro in fed and fasted rats

Orexin-A and -B (OXA, OXB) are peptides involved in many gastrointestinal (GI) functions, including motility. Orexins, their precursors and receptors are present in the GI tract. The expression of orexins increases in the hypothalamus and gastrointestinal tract in response to fasting. We have examined the effect of OXA and OXB on GI motility in vitro in fed and fasted rats. The intestinal segments were mounted in chambers filled with Krebs solution. Isotonic contractions were measured in response to acetylcholine (10-5 M), electric field stimulation (EFS), and orexins (10-9-10-7 M) alone or in the presence of orexin-1 type receptor antagonist, SB- 334867 (10-5 M), tetrodotoxin (TTX) 10-6 M, or atropine (10-5 M). Orexins caused a dose-dependent increase of intestinal segment contractions with a more pronounced effect of OXB over OXA. Fasting did not influence orexin-induced responses. Incubation with SB-334867 led to a marked decrease in orexin-induced contractions in OXA-treated segments, while those of OXB were not affected. Atropine diminished contractions only in fasted animals, while TTX led to a decreased response to orexins in both groups. The results show that OXB is predominant in inducing gut motility response, that the effect of orexins is not fully dependent on cholinergic and Na+ transmissions, and that involvement of other transmitters is possible.