Obstructive cholestasis alters intestinal transit in mice: role of opioid system.
Acute cholestasis is associated with increased activity of the endogenous opioid system. It is also known that opioid receptor agonists like morphine decrease the intestinal transit. The purpose of the present study was to investigate the effect of cholestasis on the small intestine transit and the possible involvement of opioid system in this phenomenon in mice. Cholestasis was induced by bile duct-ligation and intestinal transit was measured with charcoal meal and calculation of percent of transit through small intestine. The effect of chronic administration of naltrexone and acute pretreatment with morphine on intestinal transit was evaluated in bile duct-ligated (BDL) as well as unoperated (CTL) and sham-operated (SHAM) animals. The plasma alkaline phosphatase and alanine aminotransferase activities were also measured. A significant decrease in small intestine transit (%transit) was observed in BDL mice compared to SHAM animals, which was prominent even after 24 h of cholestasis. Chronic pretreatment with an opioid receptor antagonist, naltrexone, (10 mg/kg, i.p for 2, 4 or 6 days) completely restored the cholestasis-induced decrease in %transit to that of control animals. Although the acute administration of morphine (2 mg/kg, s.c.) 20 min before charcoal feeding caused a significant decrease in the intestinal transit of CTL and SHAM animals, it did not decrease the %transit of BDL animals on the day 5 after operation. Our findings show that acute cholestasis is associated with a prominent decrease in small intestine transit in mice and opioid receptors maybe involved in this phenomenon.
Ghaffari
Kamyar
K
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Savadkuhi
Shahab Tour
ST
Honar
Hooman
H
Riazi
Kiarash
K
Shafaroodi
Hamed
H
Moezi
Leila
L
Ebrahimkhani
Mohammad Reza
MR
Tahmasebi
Mohammad Saeid Radjabzadeh
MS
Dehpour
Ahmad Reza
AR
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001651:Cholestasis, Extrahepatic / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005772:Gastrointestinal Transit / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007421:Intestine, Small / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use*; D009271:Naltrexone / Q000008:administration & dosage / Q000627:therapeutic use*
D009271:Naltrexone; D009020:Morphine; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase