Stimulation of colonic motility in dogs and rats by an enkephalin analogue pentapeptide.

Hoe 825 causes contractions of the large bowel in conscious dogs, this effect was poorly dose-dependent. The stimulatory effect could be blocked by naloxone. In the pentobarbital-anaesthetized rat, Hoe 825 led to a dose-dependent increase in contractions of the large bowel with a threshold dose of 0.3-1/microgram/kg i.v. and again the effect could be blocked by naloxone. The "in vitro" preparation of the rat colon strip could be brought to contractions in a dose-dependent manner with an IC50 of 2 X 10(-10) mol/ml. This sensitive in vitro test system might be a useful and simple bioassay for enkephalins, when their gut stimulating properties are under investigation. The enkephalin peptide Hoe 825 acts via peripheral opiate receptors and does not need central nervous innervation, at least in rats. The powerful effects of Hoe 825 on the large bowel in conscious and anaesthetized animals might be of therapeutic value in humans under conditions were gut motility is missing especially in paralytic ileus.