Enhancement by methionine enkephalin of colon carcinogenesis induced by azoxymethane.
The effect of the opioid receptor agonist methionine enkephalin (Met-enkephalin) and the opioid receptor antagonist naloxone on colonic carcinogenesis induced by azoxymethane was investigated in Wistar rats. Rats received ten weekly injections of 7.4 mg/kg of body weight of azoxymethane and injections of Met-enkephalin (50 micrograms/kg of body weight), naloxone (2 mg/kg of body weight), or Met-enkephalin (50 micrograms/kg of body weight) plus naloxone (2 mg/kg of body weight) once every 2 days. In wk 40, the group treated with Met-enkephalin had a significantly increased incidence of colonic tumors. A combination of Met-enkephalin and naloxone attenuated the enhancing effect by Met-enkephalin on the development of colonic tumors. Administration of naloxone alone had no influence on colonic tumorigenesis. During and after administration of the carcinogen, the bromodeoxyuridine-labeling indices of the colon mucosa and/or cancers were significantly increased in rats treated with Met-enkephalin. However, a combination of Met-enkephalin and naloxone significantly decreased the labeling indices of the colon mucosa and/or cancers. These findings indicate that Met-enkephalin enhanced colon carcinogenesis and that naloxone attenuated this enhancement. Because naloxone is an opioid receptor antagonist, these findings also indicate that the enhancing effect of Met-enkephalin on colon carcinogenesis may be mediated through opioid receptors.
Iishi
H
H
Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan.
Tatsuta
M
M
Baba
M
M
Okuda
S
S
Taniguchi
H
H
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004744:Enkephalin, Methionine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D009270:Naloxone; D004744:Enkephalin, Methionine; D001397:Azoxymethane