Contribution of Lysosomes to the Subcellular Distribution of Basic Drugs in the Rat Liver
Identifieur interne : 002A51 ( Main/Exploration ); précédent : 002A50; suivant : 002A52Contribution of Lysosomes to the Subcellular Distribution of Basic Drugs in the Rat Liver
Auteurs : Junko Ishizaki [Japon] ; Koichi Yokogawa [Japon] ; Masako Hirano [Japon] ; Emi Nakashima [Japon] ; Yoshimichi Sai [Japon] ; Shoji Ohkuma [Japon] ; Tohru Ohshima [Japon] ; Fujio Ichimura [Japon]Source :
- Pharmaceutical Research [ 0724-8741 ] ; 1996-06-01.
Abstract
Abstract: Purpose. We examined the subcellular distribution of the basic drugs, chlorpromazine (CPZ), imipramine (IMP) and biperiden (BP), in rat liver, and evaluated the contribution of lysosome (Lys) to their intracellular distribution in comparison with that of mitochondria (Mit). Methods. In an in vivo distribution, the concentrations of CPZ, IMP and BP in the liver subcellular fractions were determined. In an in vitro study, uptake of [3H]IMP into Lys and Mit fractions was determined in the presence or absence of several agents. Results. The distribution of these drugs 10 min after administration was quite similar. However, the relative specific contents (the drug concentration per protein of each fraction divided by that of the total homogenate) in Lys were 7.3, 9.6 and 4.2, respectively for CPZ, IMP and BP, whereas those in the other organella were only 0.4 ~ 1.7. In an in vitro uptake study, the dose response of IMP uptake into Lys was biphasic, while that into Mit fractions was monophasic. The binding of IMP to the high affinity sites of Lys was pH dependent and disappeared in 50 mM NH4C1 or 50 µM CPZ, both of which increased the intralysosomal pH. the low affinity sites were not affected by these drugs. Conclusions. The results indicated that Lys has the highest affinity for the basic drugs in the liver and that its contribution to their subcellular distribution depends on the intralysosomal pH, which is also affected by these drugs. The importance of these effects may become significant in combination therapy using various basic drugs.
Url:
DOI: 10.1023/A:1016061330387
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 001988
- to stream Istex, to step Curation: 001988
- to stream Istex, to step Checkpoint: 001841
- to stream Main, to step Merge: 002B03
- to stream Main, to step Curation: 002A51
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Contribution of Lysosomes to the Subcellular Distribution of Basic Drugs in the Rat Liver</title><author><name sortKey="Ishizaki, Junko" sort="Ishizaki, Junko" uniqKey="Ishizaki J" first="Junko" last="Ishizaki">Junko Ishizaki</name></author><author><name sortKey="Yokogawa, Koichi" sort="Yokogawa, Koichi" uniqKey="Yokogawa K" first="Koichi" last="Yokogawa">Koichi Yokogawa</name></author><author><name sortKey="Hirano, Masako" sort="Hirano, Masako" uniqKey="Hirano M" first="Masako" last="Hirano">Masako Hirano</name></author><author><name sortKey="Nakashima, Emi" sort="Nakashima, Emi" uniqKey="Nakashima E" first="Emi" last="Nakashima">Emi Nakashima</name></author><author><name sortKey="Sai, Yoshimichi" sort="Sai, Yoshimichi" uniqKey="Sai Y" first="Yoshimichi" last="Sai">Yoshimichi Sai</name></author><author><name sortKey="Ohkuma, Shoji" sort="Ohkuma, Shoji" uniqKey="Ohkuma S" first="Shoji" last="Ohkuma">Shoji Ohkuma</name></author><author><name sortKey="Ohshima, Tohru" sort="Ohshima, Tohru" uniqKey="Ohshima T" first="Tohru" last="Ohshima">Tohru Ohshima</name></author><author><name sortKey="Ichimura, Fujio" sort="Ichimura, Fujio" uniqKey="Ichimura F" first="Fujio" last="Ichimura">Fujio Ichimura</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:C35141A128DE168368FD91656AB989453CA28736</idno><date when="1996" year="1996">1996</date><idno type="doi">10.1023/A:1016061330387</idno><idno type="url">https://api.istex.fr/ark:/67375/1BB-5NQ31WW2-Z/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">001988</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001988</idno><idno type="wicri:Area/Istex/Curation">001988</idno><idno type="wicri:Area/Istex/Checkpoint">001841</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">001841</idno><idno type="wicri:doubleKey">0724-8741:1996:Ishizaki J:contribution:of:lysosomes</idno><idno type="wicri:Area/Main/Merge">002B03</idno><idno type="wicri:Area/Main/Curation">002A51</idno><idno type="wicri:Area/Main/Exploration">002A51</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Contribution of Lysosomes to the Subcellular Distribution of Basic Drugs in the Rat Liver</title><author><name sortKey="Ishizaki, Junko" sort="Ishizaki, Junko" uniqKey="Ishizaki J" first="Junko" last="Ishizaki">Junko Ishizaki</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Hospital Pharmacy, Kanazawa University, 13-1 Takara-machi, 920, Kana-zawa</wicri:regionArea><wicri:noRegion>Kana-zawa</wicri:noRegion></affiliation></author><author><name sortKey="Yokogawa, Koichi" sort="Yokogawa, Koichi" uniqKey="Yokogawa K" first="Koichi" last="Yokogawa">Koichi Yokogawa</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Hospital Pharmacy, Kanazawa University, 13-1 Takara-machi, 920, Kana-zawa</wicri:regionArea><wicri:noRegion>Kana-zawa</wicri:noRegion></affiliation></author><author><name sortKey="Hirano, Masako" sort="Hirano, Masako" uniqKey="Hirano M" first="Masako" last="Hirano">Masako Hirano</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Hospital Pharmacy, Kanazawa University, 13-1 Takara-machi, 920, Kana-zawa</wicri:regionArea><wicri:noRegion>Kana-zawa</wicri:noRegion></affiliation></author><author><name sortKey="Nakashima, Emi" sort="Nakashima, Emi" uniqKey="Nakashima E" first="Emi" last="Nakashima">Emi Nakashima</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Hospital Pharmacy, Kanazawa University, 13-1 Takara-machi, 920, Kana-zawa</wicri:regionArea><wicri:noRegion>Kana-zawa</wicri:noRegion></affiliation></author><author><name sortKey="Sai, Yoshimichi" sort="Sai, Yoshimichi" uniqKey="Sai Y" first="Yoshimichi" last="Sai">Yoshimichi Sai</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biochemistry, Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, 920, Kanazawa</wicri:regionArea><wicri:noRegion>Kanazawa</wicri:noRegion></affiliation></author><author><name sortKey="Ohkuma, Shoji" sort="Ohkuma, Shoji" uniqKey="Ohkuma S" first="Shoji" last="Ohkuma">Shoji Ohkuma</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biochemistry, Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, 920, Kanazawa</wicri:regionArea><wicri:noRegion>Kanazawa</wicri:noRegion></affiliation></author><author><name sortKey="Ohshima, Tohru" sort="Ohshima, Tohru" uniqKey="Ohshima T" first="Tohru" last="Ohshima">Tohru Ohshima</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Legal Medicine, School of Medicine, Kanazawa University, Takara-machi, 13-1, 920, Kanazawa</wicri:regionArea><wicri:noRegion>Kanazawa</wicri:noRegion></affiliation></author><author><name sortKey="Ichimura, Fujio" sort="Ichimura, Fujio" uniqKey="Ichimura F" first="Fujio" last="Ichimura">Fujio Ichimura</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Hospital Pharmacy, Kanazawa University, 13-1 Takara-machi, 920, Kana-zawa</wicri:regionArea><wicri:noRegion>Kana-zawa</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Pharmaceutical Research</title><title level="j" type="sub">An Official Journal of the American Association of Pharmaceutical Scientists</title><title level="j" type="abbrev">Pharm Res</title><idno type="ISSN">0724-8741</idno><idno type="eISSN">1573-904X</idno><imprint><publisher>Kluwer Academic Publishers-Plenum Publishers</publisher><pubPlace>New York</pubPlace><date type="published" when="1996-06-01">1996-06-01</date><biblScope unit="volume">13</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="902">902</biblScope><biblScope unit="page" to="906">906</biblScope></imprint><idno type="ISSN">0724-8741</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0724-8741</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Purpose. We examined the subcellular distribution of the basic drugs, chlorpromazine (CPZ), imipramine (IMP) and biperiden (BP), in rat liver, and evaluated the contribution of lysosome (Lys) to their intracellular distribution in comparison with that of mitochondria (Mit). Methods. In an in vivo distribution, the concentrations of CPZ, IMP and BP in the liver subcellular fractions were determined. In an in vitro study, uptake of [3H]IMP into Lys and Mit fractions was determined in the presence or absence of several agents. Results. The distribution of these drugs 10 min after administration was quite similar. However, the relative specific contents (the drug concentration per protein of each fraction divided by that of the total homogenate) in Lys were 7.3, 9.6 and 4.2, respectively for CPZ, IMP and BP, whereas those in the other organella were only 0.4 ~ 1.7. In an in vitro uptake study, the dose response of IMP uptake into Lys was biphasic, while that into Mit fractions was monophasic. The binding of IMP to the high affinity sites of Lys was pH dependent and disappeared in 50 mM NH4C1 or 50 µM CPZ, both of which increased the intralysosomal pH. the low affinity sites were not affected by these drugs. Conclusions. The results indicated that Lys has the highest affinity for the basic drugs in the liver and that its contribution to their subcellular distribution depends on the intralysosomal pH, which is also affected by these drugs. The importance of these effects may become significant in combination therapy using various basic drugs.</div></front></TEI><affiliations><list><country><li>Japon</li></country></list><tree><country name="Japon"><noRegion><name sortKey="Ishizaki, Junko" sort="Ishizaki, Junko" uniqKey="Ishizaki J" first="Junko" last="Ishizaki">Junko Ishizaki</name></noRegion><name sortKey="Hirano, Masako" sort="Hirano, Masako" uniqKey="Hirano M" first="Masako" last="Hirano">Masako Hirano</name><name sortKey="Ichimura, Fujio" sort="Ichimura, Fujio" uniqKey="Ichimura F" first="Fujio" last="Ichimura">Fujio Ichimura</name><name sortKey="Nakashima, Emi" sort="Nakashima, Emi" uniqKey="Nakashima E" first="Emi" last="Nakashima">Emi Nakashima</name><name sortKey="Ohkuma, Shoji" sort="Ohkuma, Shoji" uniqKey="Ohkuma S" first="Shoji" last="Ohkuma">Shoji Ohkuma</name><name sortKey="Ohshima, Tohru" sort="Ohshima, Tohru" uniqKey="Ohshima T" first="Tohru" last="Ohshima">Tohru Ohshima</name><name sortKey="Sai, Yoshimichi" sort="Sai, Yoshimichi" uniqKey="Sai Y" first="Yoshimichi" last="Sai">Yoshimichi Sai</name><name sortKey="Yokogawa, Koichi" sort="Yokogawa, Koichi" uniqKey="Yokogawa K" first="Koichi" last="Yokogawa">Koichi Yokogawa</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002A51 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002A51 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:C35141A128DE168368FD91656AB989453CA28736
|texte= Contribution of Lysosomes to the Subcellular Distribution of Basic Drugs in the Rat Liver
}}
| This area was generated with Dilib version V0.6.33. |  |