Morphine-morphine glucuronide pools in the rat liver: effects of Triton X-100.
The purpose was to determine the effect on the morphine-morphine glucuronide systems of Triton X-100 instilled into the area of the hepatic canalicular membrane by segmented retrograde intrabiliary injection (40 microliters of 0.4% Triton + 31 microliters of saline) in the isolated in situ perfused livers of male Sprague-Dawley rats. In all experiments, [14C]morphine was given by segmented retrograde intrabiliary injection (40 microliters of [14C]morphine + 110 microliters of saline). The control single pass perfusate contained 15.8% [14C]morphine glucuronide (MG) and 6.2% [14C]morphine. With Triton, the major changes observed were an unusual plateau-like pattern of egress of the [14C]MG into the perfusate and a profound decrease in the [14C]MG excretion into bile. In controls, 45 mg of unlabeled morphine sulfate intraportally 5 min before the [14C]morphine reduced the perfusate [14C]MG and increased [14C]morphine as expected by isotope dilution. Also, [14C]MG recovery in bile was accordingly decreased (intact pentobarbital-anesthetized rat); however, the [14C]morphine in bile did not change even though intracellular availability of [14C]morphine must have been increased. In pulse chase experiments, [14C] morphine was followed in 2 min with 45 mg of morphine sulfate intraportally. The perfusate [14C]MG declined and [14C]morphine increased. However, on the canalicular side (intact pentobarbital-anesthetized rat) no isotope dilution was evident: [14C]MG and [14C]morphine content in bile was similar to controls given no morphine sulfate. Triton treatment decreased the amount of [14C] morphine which could be chased into the perfusate. Several different pools of morphine and MG exist in the liver; the canalicular and sinusoidal sites respond very differently to manipulation of these pools.
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001648:Bile Canaliculi / Q000187:drug effects / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000378:metabolism*; D009022:Morphine Derivatives / Q000378:metabolism*; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013501:Surface-Active Agents / Q000494:pharmacology*; D013997:Time Factors
D003902:Detergents; D009022:Morphine Derivatives; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D009020:Morphine; D017830:Octoxynol; C018108:morphine-3-glucuronide