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.
Institute of Pharmacology, University of Modena, Italy.
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Poggioli
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Arletti
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Vergoni
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Castelli
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Bertolini
D000818:Animals; D001646:Bile / Q000187:drug effects; D002779:Cholestasis / Q000139:chemically induced / Q000517:prevention & control*; D003248:Constipation / Q000139:chemically induced / Q000517:prevention & control*; D003366:Cosyntropin / Q000494:pharmacology*; D003672:Defecation / Q000187:drug effects; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009021:Morphine Dependence / Q000150:complications*; D051381:Rats; D011919:Rats, Inbred Strains
D003366:Cosyntropin; D009020:Morphine