ACTH-(1-24) antagonizes the cholestatic and constipating effects of morphine

In guinea-pigs and rats, ACTH-(1-24), i.m. injected in a dose-range of 10-150 micrograms/kg, dose-dependently antagonized the cholestatic effect of morphine (15 mg/kg i.m.). In guinea-pigs, however, the effect of morphine (66 +/- 7.7% bile flow) was only partially antagonized even by the highest dose of ACTH-(1-24) (89.21 +/- 3.4%), while in rats it was completely prevented by the dose of 75 micrograms/kg of ACTH. In morphine-dependent rats, ACTH-(1-24), injected i.p. at doses of 50, 100 and 150 micrograms/kg, dose-dependently increased the number of fecal pellets during the first 3 hr after treatment. These results show that ACTH antagonizes morphine in vivo at the biliary and intestinal level, and further support the idea that ACTH-MSH peptides are physiological antagonists of opioids.