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S Awazu

Publications and source records attributed to S Awazu.

At least 55 records · Page 3Linked to original sources
PubMed1988

Conformational change in plasma albumin due to interaction with isolated rat hepatocyte.

The electron spin resonance spectroscopy of 4-isothiocyanato-tempo labeled to bovine serum albumin (BSA) and the absorption spectroscopy of eosin maleimide labeled to BSA in the isolated rat hepatocyte suspension indicate conformational change occurring in the albumin molecule during interaction with the hepatocellular membrane. The conformational change in the albumin molecule may possibly accelerate the dissociation of albumin-organic anion complexes at the surface of the liver cell. The conformational change in the albumin molecule may explain in part the mechanism of albumin-mediated hepatic transport.

Animals↗
PubMed1987

Influence of the N-B transition of human serum albumin on the structure of the warfarin-binding site.

The fluorescence quantum yield of warfarin increased with the viscosity of the medium and showed good correlation with it. The internal rotation of the acetonylbenzyl group of a warfarin molecule may thus possibly decrease in a viscous medium. the fluorescence quantum yield of warfarin bound to human serum albumin increased with the pH of the medium in the pH range of 6.2-9.0. Fluorescence-emission maximum wavelengths of warfarin bound to human serum albumin indicated a small blue-shift with the pH of the medium and that of free warfarin in the absence of albumin also shifted slightly to a shorter wavelength with the viscosity of the medium. Warfarin is bound more strongly to human serum albumin at basic pH than at neutral pH, and the increase in the bound fraction of warfarin correlated well with the increase in the fluorescence quantum yield of bound warfarin in the same pH range. Thus, the structure of the warfarin-binding site in the B (base) form appears more spatially confined than that in the N (neutral) form. The motion of the warfarin molecule bound to its binding site on human serum albumin in the N-B transition may thus be more restricted at basic than at neutral pH, and this may possibly be the reason for the stronger binding of warfarin to human serum albumin in the B form.

Binding Sites↗
PubMed1987

Fluorescence energy transfer study of the relationship between the lone tryptophan residue and drug binding sites in human serum albumin.

The relationship between the lone tryptophan residue at position 214 and drug binding sites (Sites I and II) in human serum albumin (HSA) was studied by fluorescence energy transfer. The distance between the lone tryptophan residue and ligands bound to HSA was estimated by Förster's equation, taking into consideration the degree of ligand binding at these sites, as determined from binding parameters (binding constant, k, and the number of binding sites, n). For all ligands investigated, the distance in each case appeared to asymptotically decrease when the occupation ratio of the binding sites increased with ligand concentration. When the primary binding site of each ligand in HSA was almost saturated, the distance attained a constant value, making possible a somewhat more exact determination of the distance. The distance ranged from approximately 22 to 23 A for ligands typical of Site I (warfarin, dansylamide, dansylglutamine), and approximately 16.1 to 17.5 A for ligands typical of Site II (dansylsarcosine, dansylproline, dansylglycine, diazepam, flufenamic acid).

Amino Acids↗
PubMed1987

Enhancement of jejunal and colonic absorption of fosfomycin by promoters in the rat.

A means of enhancing absorption of the antibiotic, fosfomycin, has been investigated using promoters in rat jejunum and colon. Polyoxyethylene lauryl ether (BL-9EX), saponin, the sodium salts of fatty acids and mixed micelles were effective at 1% in increasing fosfomycin absorption. Of the sodium salts of saturated medium-chain fatty acids examined, the strength of this effect was in the order caprate greater than laurate greater than caprylate. Mixed micelles, consisting of fusogenic lipids and sodium taurocholate, enhanced fosfomycin absorption independently of the degree of unsaturation of the lipids; their effectiveness far exceeded that of sodium taurocholate alone. The action of these promoters was more evident in the colon than in the jejunum, except for the sodium salts of bile acids and disodium ethylenediaminetetraacetate (EDTA-2Na). The effects of glycocholate and taurocholate were essentially the same at both absorption sites, but that of EDTA-2Na was much greater in the jejunum than the colon. Improved fosfomycin absorption was observed at more than 0.5% sodium caprate concentrations in both the jejunum and colon. BL-9EX was effective at 0.1% in the jejunum or at 0.05% in the colon. The effectiveness at these low concentrations demonstrates the practicality of promoters for improving fosfomycin absorption with only minor membrane damage, especially in the colon.

Animals↗
PubMed1987

Differences in the promotion mechanism of the colonic absorption of antipyrine, phenol red and cefmetazole.

The promotion of antipyrine, phenol red and cefmetazole absorption by sodium ethylenediaminetetraacetate (EDTA-Na) as a paracellular promoter, diethyl maleate (DEM) as a transcellular promoter, and sodium taurocholate (TC-Na), whose promotion mechanism is still unclear, has been investigated by the rat in-situ colonic loop technique. All these promoters increased AP absorption and water influx from the lumen to the blood. Ouabain treatment suppressed the increase in antipyrine absorption and water influx induced by TC-Na and EDTA-Na, but did not modify the enhancing effect of DEM. Thus, the promotion mechanism of TC-Na may be similar to that of EDTA-Na. Phenol red and cefmetazole absorption were increased by TC-Na and EDTA-Na but not by DEM. Accordingly, phenol red and cefmetazole absorption appears to be promoted via paracellular but not transcellular routes. The collection of blood for plasma samples reduced the influx of water which had been increased by TC-Na or EDTA-Na. Consequently, the enhancement in antipyrine plasma concentration by these promoters was reduced to the control level. The inhibitory mechanism for this is discussed on the basis of the blood-flow limitation of antipyrine and water absorption.

Animals↗
PubMed1987

Alteration in rat liver microsomal membranes induced by acetaminophen.

Acetaminophen caused a reversible change in the fluorescence polarization of eosin maleimide and dansyl chloride labeled to rat liver microsomes, indicating that acetaminophen acts on microsomal membrane proteins. Acetaminophen in the presence of nicotinamide adenine dinucleotide phosphate (NADPH), brought about an irreversible change in the fluorescence polarization of the probes. Acetaminophen, with or without NADPH, was also found to change the fluorescence polarization of lipid-soluble fluorescent probes, 2- and 12-(9-anthroyloxy)stearic acid labeled to microsomes, indicating its action on microsomal membrane lipids.

Acetaminophen↗
PubMed1987

Aryl sulfotransferase in rat liver: multiplicity and substrate specificity.

Rat liver aryl sulfotransferase was purified by chromatography on diethylaminoethyl-cellulose or chromatofocusing and three fractions, referred to by Sekura and Jakoby as I, II and IV, were obtained in the order of their elution, each containing sulfation activity. p-Nitrophenol (PNP) at mM order and beta-naphthol were substrates common to all three fractions, but PNP at microM order and tyramine were substrates only for IV. IV corresponded to the enzyme designated M by Rein et al. and was active with monoamine, as predicted from our previous results with rat liver cytosol. However, the effectiveness of IV in bringing about the sulfation of PNP at mM order was not evident from our previous results. The characteristics of aryl sulfotransferase multiplicity on the basis of thermostability of sulfation activity could not be determined since essentially the characteristics were the same for all three purified fractions. The multiplicity of aryl sulfotransferase purified from rat liver was different from that of human platelets, indicating possible species and/or tissue differences in this enzyme.

Animals↗
PubMed1986

Effects of salicylic acid on the permeability of the plasma membrane of the small intestine of the rat: a fluorescence spectroscopic approach to elucidate the mechanism of promoted drug absorption.

The effects of sodium salicylate on the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH), 2-hydroxyoctadecanoic acid, 9-anthroate (2-AS), 12-hydroxyoctadecanoic acid, 9-anthroate (12-AS), 8-anilino-1-naphthalenesulfonic acid (ANS) and 2',4',5',7'-tetrabromo-5-maleimidofluorescein, disodium salt (EM), with which rat small intestinal brush border membrane vesicles were labeled, were examined. Salicylate ion decreased the fluorescence polarization of ANS and EM in these vesicles, however, it had no influence on the fluorescence polarization of DPH, 2-AS and 12-AS-labeled vesicles. It also released trapped 6-carboxyfluorescein (3',6'-dihydroxy-3-oxospiro-[phthalan-1,9'-xanthene]-6-carbo xylic acid) (CF) from the vesicles, but caused no leakage of trapped CF from liposomes. These results indicate that salicylate ion increases the plasma membrane permeability by effecting the plasma membrane proteins rather than directly interacting with the membrane lipids. The action of salicylate ion on these vesicles could possibly promote nonabsorbable drug absorption in vivo.

Animals↗
PubMed1986

Factors influencing the tissue distribution of coenzyme Q10 intravenously administered in an emulsion to rats: emulsifying agents and lipoprotein lipase activity.

The tissue distribution of coenzyme Q10 (CoQ10) administered intravenously in an emulsion prepared with egg yolk phosphatidylcholine (PC), egg yolk sphingomyelin (SPM) or a combination of PC and a polyoxyethylene derivative of hydrogenated castor oil (HCO-60) (PC + HCO-60) was investigated. The disappearance from the plasma of CoQ10 administered in three different emulsions of lipid particle size less than 0.5 micron varied with the particular emulsifier. Its disappearance occurred most rapidly from the PC emulsion; with the addition of HCO-60, its disappearance was much slower. In the reticuloendothelial system, the concentration of CoQ10 was higher in the spleen, for both the SPM and PC + HCO-60 emulsions than for the PC emulsion. HCO-60 reduced the CoQ10 distribution in the liver from the PC emulsion. Differences in disappearance rates from the plasma are thus considered to be due to the extent of CoQ10 distribution in the liver. CoQ10 concentration in the heart, a target organ, was greatest with the PC emulsion. Its distribution was related to lipoprotein lipase (LPL) activity in this organ. The effects caused by HCO-60, however, could not be explained by LPL activity alone. CoQ10 distribution in the adrenal gland and kidney can be explained partly by LPL activity but in the presence of HCO-60, the distribution mechanism apparently involves other factors.

Animals↗
PubMed1986

Heterogeneous distribution of the conjugation activity of acetaminophen and p-nitrophenol in isolated rat liver cells.

The uneven distribution of the glucuronidation and sulfation activity of acetaminophen (APAP) and p-nitrophenol (PNP) in liver was studied using centrilobular and periportal regions of isolated rat hepatocytes obtained by Percoll density gradient centrifugation, in a manner similar to that for harmol reported previously. The glucuronidation of APAP and PNP occurred predominantly in the periportal region. Glucuronidation activity of APAP in the centrilobular region was not detected. This finding may reflect the existence of different forms of uridine diphosphate-glucuronyltransferase (UDPGT) for APAP and PNP. The regional difference in Km values was observed for PNP, but not for harmol as reported in the previous paper. This suggests the existence of multiple forms of UDPGT for PNP as well as the heterogeneous distribution of this enzyme in liver lobules. The sulfation rates of APAP and PNP in the centrilobular region were smaller than those in the periportal region. The regional difference of APAP sulfation was due to different Vmax values. As shown in the harmol experiment, the predominant distribution of sulfation activity of APAP and PNP in the periportal region agreed with the results in the perfused liver previously reported by other investigators but that of glucuronidation activity was at variance with them.

Acetaminophen↗
PubMed1986

Characterization of the interaction of albumin with isolated rat liver cells to reveal the mechanism of albumin-mediated hepatic transport.

The binding of bovine serum albumin (BSA), containing 125I-BSA, to isolated rat hepatocytes was studied over a 300-fold concentration range of BSA to characterize the interaction between albumin and the liver cells in albumin-mediated hepatic transport. The binding of BSA with a high affinity to the cell surface of hepatocytes was not found in the binding behavior. The bound fraction of BSA with hepatocytes was about 1% over those concentration range of BSA.

Animals↗
PubMed1985

Fluorescence study on the interaction of salicylate with rat small intestinal epithelial cells: possible mechanism for the promoting effects of salicylate on drug absorption in vivo.

The water-soluble drug, salicylate, was rapidly taken up by rat small intestinal epithelial cells. Salicylate, known to enhance the absorption of poorly absorbable drugs by rectum and small intestine, caused a significant decrease in the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and a slight increase in the fluorescence polarization of 8-anilino-1-naphthalene sulfonic acid (ANS) in the isolated rat small intestinal epithelial cell suspension. An increase in the membrane fluidity of epithelial cells may possibly contribute to the enhancement of drug absorption by salicylate.

Anilino Naphthalenesulfonates↗
PubMed1985

The promotion of drug rectal absorption by water absorption.

The promotion of the rectal absorption of antipyrine by sodium taurocholate (TC-Na) or sodium ethylenediaminetetraacetate (EDTA-Na) has been examined by in-situ recirculating perfusion in the rat. These promoters significantly increased water influx, efflux and antipyrine absorption clearance (CLAP). Ouabain treatment significantly reduced the increase in both rectal absorption of drug and water flux. Water absorption dependent on active sodium transport may thus possibly promote the rectal absorption of poorly absorbable drugs.

Animals↗
PubMed1985

Promoting mechanism by bile salt related to water absorption in drug rectal absorption.

The promoting mechanism by bile salts in rat rectal absorption of antipyrine was studied by the in situ recirculating perfusion. The significant correlation between rectal absorption clearance (CLAP) of antipyrine (AP) and apparent water influx (influx') was found in the control without promoters, indicating the existence of solvent drag in the AP rectal absorption. Sieving coefficient of AP (bAP), i.e. the slope of the regression line between CLAP and influx', was 0.6 approximately equal to that in small intestine reported previously. The relation between the promoting effects and solvent drag was further studied, resulting that both CLAP and influx' were significantly enhanced by sodium taurocholate (TC-Na), sodium glycocholate (GC-Na) and sodium cholate (C-Na). Accordingly the promoting effects of bile salts might be due to the increase in solvent drag. However TC-Na did not produce the significant change in bAP. From these results, the enhancing mechanism in the epithelial cell membrane transport was discussed.

Animals↗