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Biomedical subjects

J M Fujimoto

Publications and source records attributed to J M Fujimoto.

At least 91 records · Page 5Linked to original sources
PubMed1980

Absence of cross-tolerance to heroin in morphine-tolerant mice.

Mice implanted with morphine pellets demonstrated a 30-fold increase in tolerance to subcutaneously administered morphine but showed no cross-tolerance to subcutaneously administered heroin. When given morphine intracerebroventricularly, the mice showed no tolerance to morphine or cross-tolerance to heroin. These observations depended on the presence of the morphine pellet. If the pellets were removed prior to determinations of potency, the expected responses--tolerance to morphine and cross-tolerance to heroin--were obtained. The blood-brain barrier may be a prime site for the expression of morphine tolerance in mice.

Animals↗
PubMed1980

Transit patterns of marker compounds given by segmented retrograde intrabiliary injection (SRII) in the isolated in situ perfused rat liver.

The mode of transfer of solutes across the biliary tree epithelium in the reabsorptive direction was studied by the segmented retrograde intrabiliary injection technique in isolated perfused liver of rats. The main purpose was to study the pattern of transit of the radioactive marker compounds through the liver into the venous perfusate. The perfusate was collected as a single pass. All of the marker compounds were quantitatively accounted for in the bile and the perfusate. The apparent volumes of distribution of dextran and sucrose were smaller than that for erythritol. Mannitol was similar to erythritol. The mean transit times were correspondingly: dextran congruent to sucrose < mannitol congruent to erythritol. Dehydrocholate (100 mumol/kg) had no effect on these parameters, but taurocholate (100 mumol/kg) increased the mean transit time for sucrose. This effect was probably related to an increase in biliary tree permeability produced by taurocholate. The present approach appeared to be useful in assessing hepatobiliary function and its alteration by allowing the transit patterns of compounds to be determined in passing from bile through the liver to the blood.

Animals↗
PubMed1980

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.

Animals↗
PubMed1980

A new mode of action of SKD 525-A on morphine disposition studied by segmented retrograde intrabiliary injection (SRII) in the isolated in situ perfused rat liver.

The effect of SKF-525-A on the disposition of morphine given by segmented retrograde intrability injection (SRII) was studied in the isolated in situ perfused livers of Sprague-Dawley male rats. SRII of morphine repeated after treatment SKF 525-A (20 mg/kg b. wt. intraportally) showed decreased recovery of morphine glucuronide (MG) in the bile and in the venous outflow. On the other hand, morphine in the venous outflow was increased. Thus, SKF 525-A decreased the total recovery (bile plus venous outflow) of MG. The results after intraportal administration of morphine were consistent with these observations by SRII. These results might indicate inhibition of conjugation by SKF 525-A. However, a similar effect of SKF 525-A was obtained when MG was given by either route. These latter results were interpreted to mean tht SKF 252-A affected a translocation process for MG. Analysis of the liver after the SRII of MG indicated that SKF 525-A caused a 10-fold increase in retention of MG in the liver. Based on the cumulative venous outflow curves, the difference in apparent volumes of distribution, Q, indicated that morphine was taken up by hepatocytes beyond the mannitol, total liver water (intra- and extracellular) space and SKF 525-A decreased this apparent volume of distribution of morphine. Also, SKF 525-A increased the apparent volume of distribution of MG. The mean transit time of morphine was not altered by SKF 525-A whereas that of MG became longer. The evidence indicated that SKF 525-A decreased the egress of MG from liver, a newly recognized mode of action of SKF 525-A.

Animals↗
PubMed1975

Narcotic antagonist activity of several metabolites of naloxone and naltrexone tested in morphine dependent mice (38558).

A rabbit liver enzyme system was used to produce the 6beta-OH reduced metabolites of naloxone and naltrexone. GC analysis indicated the presence of some 6alpha-OH metabolite in these samples. The narcotic antagonist activity of these 6beta-OH metabolite samples were compared to naloxone, naltrexone and standard 6alpha-OH naltrexone (EN-2260A) using the jumping response of morphine pellet implanted mice. For the naloxone series, the potencies were: Naloxone greater than EN 2265A greater than 6 beta-OH maloxone. For the naltrexone series: Naltrexone greater than EN 2260A greater than beta-OH naltrexone. The low potency of the reduced metabolites the rapid onset of action of the parent compounds militate against the formation of these metabolites contributing substantially to the overall narcotic antagonist action of the parent compounds.

Animals↗
PubMed1975

A study of absorption of compounds from the rat biliary tree by retrograde intrabiliary injection (RII).

Absorption of compounds from the biliary tree of rats was studied by a retrograde intrabiliary injection (RII) technique. After RII of a number of compounds in volumes that exceeded the maximum distended capacity of the biliary tree, only that volume of RII solution which corresponded to biliary tree capacity remained therein. Furthermore, this latter portion of RII solution was absorbed by a first-order process when the duration of bile duct cannula occlusion was extended. Thus, the present study demonstrates that absorption of retrogradely injected compounds continues during occlusion. Since excretion of i.v. administered compounds into the biliary system was also shown to continue during occlusion, we propose in the present study a concept of bidirectional exchange of solute within the biliary tree during occlusion. As an additional finding, after RII and occlusion, a temporary increase in bile flow was obtained. If the occlusion duration was 3 minutes or less, the bile flow response was of sufficient magnitude to repay alomst exactly the volume of bile that would have been expected to be produced. If the occlusion was 6 and 9 minutes the increased magnitude of the bile flow response was not great enough to repary the larger bile volumes expected and underpayments of -48 and -96 mul were incurred.

Absorption↗