Site of action of dehydrocholate in inhibiting the biliary excretion of morphine in the isolated in situ perfused rat liver.

Even though dehydrocholate (DHC) produced an intense choleresis, we found in the rat that the biliary excretion of morphine was inhibited by DHC. The site of action for this inhibitory effect of DHC was investigated in isolated perfused livers in conjunction with intraportal and segmented retrograde intrabiliary injecton of [14C]morphine and [14C]morphine glucuronide (MG). After segmented retrograde intrabiliary injection of morphine, DHC treatment was shown to decrease the amount of MG recovered in bile but increase the amount of MG which appeared in the blood perfusate. That this effect was due to DHC affecting the transport of MG rather than inhibition of the metabolic conjugation of morphine to MG was directly demonstrated. DHC reduced the recovery of MG in bile after administration of MG by SRII. Also in vivo, DHC decreased the recovery of bile of MG give, i.v. DHC produced no consistent effect on the apparent volume of distribution and transit time for morphine and MG and no effect on these transfer parameters for morphine-3-ethereal sulfate. Thus, the effect of DHC can with some degree of specificity be ascribed to an effect on the transport of MG from liver to bile.