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H Takikawa

Publications and source records attributed to H Takikawa.

At least 19 recordsLinked to original sources
PubMed1999

Enzymatic resolution of (+/-)-gamma-cyclohomogeraniol and conversion of its (S)-isomer to (S)-gamma-coronal, the ambergris odorant.

Enzymatic acetylation of (+/-)-gamma-cyclohomogeraniol[2-(2',2'-dimethyl-6'-methylenecyc lohexyl)ethanol] with vinyl acetate in the presence of lipase AK yielded the acetate of its (R)-isomer, leaving its (S)-isomer intact. The (S)-isomer was chemically converted to (S)-gamma-coronal[2-methylene-4-(2',2'-dimethyl-6'-methylenecyclohexy l)butanal], the ambergris odorant.

Acyclic Monoterpenes↗
PubMed1998

Effects of organic anions and bile acid conjugates on biliary excretion of pravastatin in the rat.

PURPOSE: Biliary organic anion excretion is mediated by an ATP-dependent primary active transporter, a so-called canalicular multispecific organic anion transporter (cMOAT). As there appear to be many canalicular organic anion transports, we examined the effects of various organic anions and bile acid conjugates on the biliary excretion of pravastatin in rats. METHODS: [14C]pravastatin was intravenously injected into rats with bile drainage in the presence and absence of the continuous infusion of organic anions and bile acids, and radioactivity of its biliary excretion was studied. RESULTS: Biliary excretion of [14C]pravastatin was markedly inhibited by sulfobromophthalein-glutathione, taurolithocholate-3-sulfate, ursodeoxycholate-3, 7-sulfate, and ursodeoxycholate-3-O-glucuronide. In contrast, dibromosulfophthalein only slightly inhibited biliary pravastatin excretion, and cefpiramide did not affect biliary pravastatin excretion. CONCLUSIONS: These findings further support the multiplicity of canalicular organic anion transport, and pravastatin is considered to be excreted through a canalicular transporter which is absent in EHBR in addition to through cMOAT.

Animals↗
PubMed1998

Enhanced biliary excretion of lithocholate-3-sulfate by ursodeoxycholate-3,7-disulfate infusion in Eisai hyperbilirubinemic rat (EHBR).

Biliary excretion of lithocholate-3-sulfate and ursodeoxycholate 3,7-disulfate is markedly impaired in EHBR. In the present study, the effects of ursodeoxycholate 3,7-disulfate infusion on lithocholate-3-sulfate excretion were studied in EHBR and Sprague-Dawley rats. Although in control rats, ursodeoxycholate 3,7-disulfate infusion had no effect on biliary lithocholate-3-sulfate excretion, in EHBR it enhanced biliary lithocholate-3-sulfate excretion. Although ursodeoxycholate 3,7-disulfate dose-dependently inhibited lithocholate-3-sulfate binding by rat serum albumin and rat liver cytosol, it did not affect the serum clearance of lithocholate-3-sulfate in EHBR in vivo. These findings indicate that in EHBR, in which the major ATP-dependent organic anion transporter is impaired, the excretory pathway for ursodeoxycholate 3,7-disulfate may interact to that for lithocholate-3-sulfate.

Animals↗
PubMed1998

Changes in biliary excretory mechanisms in rats with ethinyloestradiol-induced cholestasis.

Several excretory pathways for cholephilic compounds have been known. To examine the changes in excretory pathways in cholestasis induced by ethinyloestradiol, various bile acids, organic anions and organic cations were intravenously administered to ethinyloestradiol-treated rats and their biliary excretion was studied. Biliary excretion of taurocholate was slightly delayed, but its excretory maximum was markedly decreased. Biliary excretion of lithocholate-3-O-glucuronide, leukotriene C4, sulphobromophthalein and pravastatin was markedly impaired to a similar extent. Biliary excretion of vinblastine, a P-glycoprotein substrate, was increased, suggesting increased expression of P-glycoprotein. In contrast, biliary excretion of erythromycin, a cationic antibiotic, was markedly impaired. In conclusion, ethinyloestradiol treatment altered the biliary excretion of organic compounds, which may partly be related to changes of the canalicular transporters.

Animals↗
PubMed1998

Effects of colchicine and phenothiazine on biliary excretion of organic anions in rats.

Vesicular transport inhibitors have been reported to inhibit biliary excretion of some organic anions, suggesting that vesicular transport has a role in intracellular transport of these compounds. However, these inhibitors are substrates for P-glycoprotein. To examine whether P-glycoprotein has a role in canalicular transport of organic anions in addition to the canalicular multispecific organic anion transporter, we studied the effect of colchicine, a vesicular transport inhibitor, and phenothiazine to increase P-glycoprotein expression on biliary excretion of various organic anions in rats. Colchicine treatment slightly but significantly inhibited biliary excretion of indocyanine green, dinitrophenyl-glutathione and pravastatin, and had no effect on biliary excretion of sulphobromophthalein and dibromosulphophthalein. Phenothiazine treatment did not affect biliary excretion of indocyanine green and pravastatin, but it increased biliary sulphobromophthalein-glutathione excretion. In conclusion, the present findings suggest that P-glycoprotein plays an additive role on biliary excretion of some organic anions in addition to the canalicular multispecific organic anion transporter.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Primary sclerosing cholangitis in Japan--analysis of 192 cases.

Primary sclerosing cholangitis is very rare in Japan. The aim of the present study was to identify the characteristics of such patients in Japan. A questionnaire was sent to the members of the Japanese Society of Gastroenterology and responses for 192 cases were analyzed. There was male predominancy (61%), and two peaks in the age distribution at diagnosis (20-30 years and 50-70 years). Bile duct damage was mainly intra + extrahepatic (69%) versus intrahepatic (17%) or extrahepatic (14%). The incidences of eosinophilia and positivity for anti-nuclear antibody were 27% and 30%, respectively. The incidence of associated inflammatory bowel disease was 21% (38 ulcerative colitis and 2 Crohn's disease). Chronic pancreatitis, gallstones, and biliary cancers occurred in 15%, 12%, and 4%, respectively, of the 192 patients. Patients less than 40 years of age had a higher incidence than the patients 40 years old or more of damage intra + extrahepatic bile ducts (89% vs 56%) and of associated ulcerative colitis (36% vs 9%), whereas the incidence of chronic pancreatitis was lower in patients aged less than 40 years (4%). The characteristics of patients with primary sclerosing cholangitis in Japan differ from those in other countries in regard to age distribution and the incidence of complications, and at least two different groups of patients seem to exist in terms of the degree of bile duct damage and the incidence of complications.

Adult↗
PubMed1997

Effects of organic anions and bile acid conjugates on biliary excretion of LTC4 in the rat.

Biliary organic anion excretion is mediated by an ATP-dependent primary active transporter, so-called canalicular multispecific organic anion transporter (cMOAT). On the other hand, a multiplicity of canalicular organic anion transport has been suggested. Therefore, to examine the substrate specificity of cMOAT using inhibition of excretion of [3H] LTC4-derived radioactive products in the bile as a marker, we examined the effects of various organic anions and bile acid conjugates on the biliary excretion of LTC4 in rats. Biliary excretion of the metabolites of [3H] LTC4, which was injected via the femoral vein, was markedly inhibited by sulfobromophthalein-glutathione, taurolithocholate-3-sulfate, and ursodeoxycholate-3-O-glucuronide. In contrast, dibromosulfophthalein and cefpiramide slightly inhibited, and pravastatin, taurocholate, and 3,7-sul-UDC did not affect biliary LTC4 excretion. Furthermore, vinblastine and phenothiazine, a P-glycoprotein substrate and inducer, did not affect biliary LTC4 excretion. Among various organic anions and bile acid conjugates, LTC4, sulfobromophthalein-glutathione, taurolithocholate-3-sulfate, and ursodeoxycholate-3-O-glucuronide may be good substrates for cMOAT.

Animals↗
PubMed1997

Effect of tauro-alpha-muricholate and tauro-beta-muricholate on oestradiol-17 beta-glucuronide-induced cholestasis in rats.

The effect of tauro-beta-muricholate (beta MC-tau) and tauro-alpha-muricholate (alpha MC-tau) on oestradiol-17 beta-glucuronide (E217G)-induced cholestasis was compared with that of tauroursodeoxycholate (UDC-tau) in rats. Like UDC-tau, alpha MC-tau and beta MC-tau infused at the rate of 0.2 mumol/min per 100 g bodyweight (BW) completely inhibited the cholestasis induced by E217G infused at the rate of 0.06 mumol/min per 100 g BW for 20 min. These findings indicate that beta MC-tau and alpha MC-tau are useful in protecting against various types of experimental cholestasis, as well as against bile acid-induced cholestasis.

Animals↗
PubMed1997

Absorption of unconjugated bile acids and tauroursodeoxycholate in the rat intestine.

The absorption of ursodeoxycholate and its tauro-conjugate by the jejunum and the terminal ileum of rat intestine was compared with that of other unconjugated bile acids and taurocholate. In the ligated jejunum, the efficacy of absorption of unconjugated bile acids was in the following order: ursodeoxycholate = deoxycholate > chenodeoxycholate = cholate > lithocholate. This order cannot be explained by the theory that the passive diffusion of bile acids is faster the less hydroxyl bonds in the molecule. These findings on the unconjugated bile acids in the ligated jejunum were further confirmed by perfusion experiments. In the ligated terminal ileum, ursodeoxycholate, cholate and deoxycholate were absorbed as fast as taurocholate or tauroursodeoxycholate, whereas absorption of chenodeoxycholate was significantly slower. The Na+-dependency of the absorption of ursodeoxycholate and cholate in the terminal ileum was confirmed by perfusion studies. In conclusion, intestinal absorption of ursodeoxycholate was efficient in both the jejunum and ileum and these results may contribute to the high availability of ursodeoxycholate in various hepatobiliary diseases.

Animals↗
PubMed1997

Effect of taurolithocholate-3-sulphate on biliary excretion of sulphobromophthalein and dibromosulphophthalein in the Eisai hyperbilirubinaemic rat.

We previously reported that biliary lithocholate-3-sulphate excretion was inhibited by dibromosulphophthalein, not by sulphobromophthalein in Eisai hyperbilirubinaemic rats (EHBR); instead its excretion was inhibited by both organic anions in control rats. In the present study, the effect of taurolithocholate-3-sulphate on the excretion of sulphobromophthalein and dibromosulphophthalein was studied in EHBR and control Sprague-Dawley rats. Taurolithocholate-3-sulfate infusion inhibited biliary excretion of sulphobromophthalein and dibromosulphophthalein in both EHBR and control rats. These findings indicate that in control rats biliary excretion of taurolithocholate-3-sulphate is mediated by a carrier common for both organic anions, and that in EHBR, in which the canalicular multispecific organic anion transporter is impaired, the excretory pathway for taurolithocholate-3-sulphate is also partly identical to that for both organic anions.

Animals↗
PubMed1996

Evidence that interference with binding to hepatic cytosol binders can inhibit bile acid excretion in rats.

We previously identified that Y' bile acid binders (3alpha-hydroxysteroid dehydrogenases) interact with bile acids in intact rat hepatocytes using [3beta-3H, C24-14C]bile acids and that indomethacin, a competitive inhibitor of 3alpha-hydroxysteroid dehydrogenase, inhibits 3H-loss from the C3-position of bile acids as well as inhibits hepatic bile acid removal and excretion. To study the kinetics of these inhibitory effects, glycocholate transport was studied in the absence and presence of indomethacin in the single-pass perfused rat liver. Indomethacin decreased net hepatic glycocholate uptake in the perfused liver, which was confirmed in isolated hepatocytes and basolateral liver plasma membrane vesicles. However, indomethacin markedly increased the sinusoidal efflux and decreased the biliary excretion of glycocholate in the perfused liver. These observations indicate that the effect of indomethacin to delay biliary glycocholate excretion is related to either intracellular or canalicular glycocholate transport. The latter possibility seemed unlikely because indomethacin did not inhibit electrogenic or adenosine triphosphate (ATP)-dependent glycocholate uptake by canalicular liver plasma membrane vesicles. Thus, the current data support an important role for binding of bile acids to cytosolic proteins in overall hepatic transport and suggest that specific interference with cytosolic binding can interfere with the excretion of bile acids.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Alterations in glutathione homeostasis in mutant Eisai hyperbilirubinemic rats.

Eisai hyperbilirubinemic rats (EHBR) are mutant Sprague-Dawley rats that exhibit impaired biliary organic anion and reduced glutathione (GSH) secretion. In addition, liver GSH levels are twice that of age-matched controls. The mechanisms for the defect in biliary GSH secretion and the increase in cell GSH are not fully understood. We previously showed that canalicular membrane-enriched vesicles isolated from EHBR livers exhibited normal GSH transport. In the present study, we examined the steady-state rat canalicular reduced glutathione transporter (RcGshT) messenger RNA (mRNA) and protein levels, as well as the mechanisms for the increase in cell GSH. Both Northern and Western blot analyses of EHBR livers showed nearly identical RcGshT mRNA and polypeptide levels, respectively, as compared with controls. Treatment with phenobarbital, which increased steady-state RcGshT mRNA by five- to sixfold, RcGshT polypeptide, and biliary GSH secretion by onefold in controls, had a smaller effect on steady-state RcGshT-mRNA level in EHBR (by 1.5-fold) and did not increase RcGshT polypeptide or biliary GSH secretion. In examining possible mechanisms for increased liver GSH, both cysteine level and gamma-glutamylcysteine synthetase (GCS) activity were significantly higher than controls, while the activity of GSH synthetase was unchanged. Northern and Western blot analyses also showed increased steady-state GCS heavy subunit (GCS-HS) mRNA and polypeptide levels, respectively. In addition to liver, GSH levels in kidney, duodenal, jejunal, and ileal mucosa of EHBR were 200% to 300% of age-matched control rats. GCS activity was also increased in kidney cytosol of EHBR. Thus, the defect in biliary GSH secretion in EHBR most likely is either at the posttranslational level of RcGshT or in the inhibition exerted by retained endogenous organic anions. In addition, there is a widespread up-regulation of GSH synthesis capacity in the tissues of EHBR.

Analysis of Variance↗
PubMed1996

Effects of ursodeoxycholate and its conjugates on biliary glutathione excretion in rats.

The effects of ursodeoxycholate and its conjugates on biliary glutathione excretion were studied in rats. Ursodeoxycholate had no effect on glutathione excretion, but tauroursodeoxycholate (10 mumol/100 g body wt) transitionally increased biliary glutathione excretion. Ursodeoxycholate-3-O-glucuronide (2 and 10 mumol/100 g body wt) markedly inhibited biliary glutathione excretion, but ursodeoxycholate-3-sulfate (2 mumol/100 g body wt) and ursodeoxycholate-3,7-disulfate (10 mumol/100 g body wt) did not. These findings indicate the existence of several biliary excretion pathways for bile acid glucuronides and sulfates and that one of them for the glucuronides is shared by biliary glutathione excretion.

Animals↗
PubMed1996

Changes in biliary excretory mechanisms in bile duct-ligated rat.

The effects of bile duct ligation on biliary excretion of bile acids, glutathione, and lipids were studied in the rat. The bile duct of the rat was ligated for three days. The biliary bile acid excretion after bile duct cannulation was higher at first, but after 90 min became lower than that in the control rat. The bile flow in the bile duct-ligated rat was higher after bile duct cannulation and gradually decreased to the same level as in the control rat. Biliary glutathione excretion, which has been suggested to be a driving force for the bile acid-independent canalicular bile flow, was markedly decreased in the bile duct-ligated rat. The mannitol clearance was increased and the bile ductules showed proliferation in the bile duct-ligated rat, suggesting an increase in the ductular bile flow. Biliary excretion of lithocholate glucuronide was more markedly impaired than that of taurocholate. When taurocholate was infused at higher rates, which increases bile flow and biliary excretion of bile acid and lipids in the control rat, biliary bile acid and lipid excretion remained constant in the bile duct-ligated rat. These findings indicate that, in the bile duct-ligated rat, the ductular bile flow was increased and bile acid-independent canalicular bile flow was decreased and that, although the biliary excretion of bile acids was not as impaired as that of organic anions, the capacity of bile acid and lipid excretion was markedly decreased.

Animals↗