The opioid peptide analog D-Ala2-Met-enkephalinamide decreases bile flow by a central mechanism.

The existence of an opioid central pathway that may regulate bile secretion was explored by studying the effect of the intracisternal (i.c.) administration of the opiate D-Ala2-Met-enkephalinamide (DAME) on bile secretion in anesthetized male rats. The i.c. administration of DAME was associated with a dose-related decrease in bile flow that ranged from 12% to 41%, which was prevented by the opiate antagonist naloxone. Bicarbonate secretion into bile decreased significantly after i.c. DAME. Chemical adrenergic denervation and cholinergic pharmacological blockade with atropine did not prevent the DAME-induced decrease in bile flow. The data support the existence of an opioid-mediated pathway that starts in the brain and that contributes to the regulation of bile secretion.