The potential role of lysosomes in tissue distribution of weak bases
Identifieur interne : 003232 ( Main/Exploration ); précédent : 003231; suivant : 003233The potential role of lysosomes in tissue distribution of weak bases
Auteurs : Anna C. Macintyre [Australie] ; David J. Cutler [Australie]Source :
- Biopharmaceutics & Drug Disposition [ 0142-2782 ] ; 1988-11.
English descriptors
- Teeft :
- Accumulation, Accumulation ratio, Acid phosphatase, Active transport, Active uptake process, Binding sites, Biochem, Concentration dependence, Cutler, Disposit, Drug metab, Effluxable pool, Energy dependence, Energy reserves, Hepatocytes, High concentrations, Homogenate, Homogenate binding studies, Homogenization, Imipramine, Important mechanism, Intralysosomal, Large proportion, Lysosomal, Lysosomal membrane, Lysosomal volume, Lysosome, Macintyre, Metab, Metabolic inhibitors, Nonlinear, Nonlinear disposition, Perfused, Perfused liver, Perfused lung, Pharmacol, Phospholipid, Predominant mechanism, Previous section, Propranolol, Propranolol accumulation, Saturable, Saturable binding, Several studies, Structural integrity, Subcellular distribution studies, Tissue components, Weak base, Weak base accumulation, Weak bases.
Abstract
The potential importance of lysosomes as a site of accumulation of weak bases in tissues is discussed. A simple mathematical treatment predicts the quantitative significance of lysosomal trapping for monoacidic and diacidic weak bases. The features which are characteristics of lysosomal trapping are discussed, particularly in comparison with active transport and intracellular binding mechanisms. These features include: linear accumulation at low concentrations; nonlinearity at higher concentrations; dependence on structural integrity of tissue; energy dependence and competition with other weak bases. Subcellular distribution studies have previously shown that weak bases accumulate extensively in membranes; however, the dependence of accumulation on the structural integrity of tissue suggests that this is not the only significant mechanism of accumulation. The results of a range of studies of tissue distribution of weak bases are discussed to illustrate that these findings are consistent with accumulation in lung and liver being attributable to a combination of lysosomal trapping and accumulation in membranes whereas, in muscle, accumulation in membranes is the predominant mechanism of accumulation. The possible pharmacokinetic significance of lysosomal trapping of weak bases is also discussed.
Url:
DOI: 10.1002/bod.2510090602
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 000E87
- to stream Istex, to step Curation: 000E87
- to stream Istex, to step Checkpoint: 001F94
- to stream Main, to step Merge: 003303
- to stream Main, to step Curation: 003232
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">The potential role of lysosomes in tissue distribution of weak bases</title><author><name sortKey="Macintyre, Anna C" sort="Macintyre, Anna C" uniqKey="Macintyre A" first="Anna C." last="Macintyre">Anna C. Macintyre</name></author><author><name sortKey="Cutler, David J" sort="Cutler, David J" uniqKey="Cutler D" first="David J." last="Cutler">David J. Cutler</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:BD4BBD782E017013EC5048D0744C4C0162F7AC94</idno><date when="1988" year="1988">1988</date><idno type="doi">10.1002/bod.2510090602</idno><idno type="url">https://api.istex.fr/ark:/67375/WNG-L7PTN9JW-7/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000E87</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000E87</idno><idno type="wicri:Area/Istex/Curation">000E87</idno><idno type="wicri:Area/Istex/Checkpoint">001F94</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">001F94</idno><idno type="wicri:doubleKey">0142-2782:1988:Macintyre A:the:potential:role</idno><idno type="wicri:Area/Main/Merge">003303</idno><idno type="wicri:Area/Main/Curation">003232</idno><idno type="wicri:Area/Main/Exploration">003232</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">The potential role of lysosomes in tissue distribution of weak bases</title><author><name sortKey="Macintyre, Anna C" sort="Macintyre, Anna C" uniqKey="Macintyre A" first="Anna C." last="Macintyre">Anna C. Macintyre</name><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pharmacy, University of Sydney, N.S. W. 2006</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Cutler, David J" sort="Cutler, David J" uniqKey="Cutler D" first="David J." last="Cutler">David J. Cutler</name><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pharmacy, University of Sydney, N.S. W. 2006</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Correspondence address: Department of Pharmacy, University of Sydney, N.S. W. 2006</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Biopharmaceutics & Drug Disposition</title><title level="j" type="alt">BIOPHARMACEUTICS AND DRUG DISPOSITION</title><idno type="ISSN">0142-2782</idno><idno type="eISSN">1099-081X</idno><imprint><biblScope unit="vol">9</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="513">513</biblScope><biblScope unit="page" to="526">526</biblScope><biblScope unit="page-count">14</biblScope><publisher>John Wiley & Sons, Ltd.</publisher><pubPlace>New York</pubPlace><date type="published" when="1988-11">1988-11</date></imprint><idno type="ISSN">0142-2782</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0142-2782</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Accumulation</term><term>Accumulation ratio</term><term>Acid phosphatase</term><term>Active transport</term><term>Active uptake process</term><term>Binding sites</term><term>Biochem</term><term>Concentration dependence</term><term>Cutler</term><term>Disposit</term><term>Drug metab</term><term>Effluxable pool</term><term>Energy dependence</term><term>Energy reserves</term><term>Hepatocytes</term><term>High concentrations</term><term>Homogenate</term><term>Homogenate binding studies</term><term>Homogenization</term><term>Imipramine</term><term>Important mechanism</term><term>Intralysosomal</term><term>Large proportion</term><term>Lysosomal</term><term>Lysosomal membrane</term><term>Lysosomal volume</term><term>Lysosome</term><term>Macintyre</term><term>Metab</term><term>Metabolic inhibitors</term><term>Nonlinear</term><term>Nonlinear disposition</term><term>Perfused</term><term>Perfused liver</term><term>Perfused lung</term><term>Pharmacol</term><term>Phospholipid</term><term>Predominant mechanism</term><term>Previous section</term><term>Propranolol</term><term>Propranolol accumulation</term><term>Saturable</term><term>Saturable binding</term><term>Several studies</term><term>Structural integrity</term><term>Subcellular distribution studies</term><term>Tissue components</term><term>Weak base</term><term>Weak base accumulation</term><term>Weak bases</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The potential importance of lysosomes as a site of accumulation of weak bases in tissues is discussed. A simple mathematical treatment predicts the quantitative significance of lysosomal trapping for monoacidic and diacidic weak bases. The features which are characteristics of lysosomal trapping are discussed, particularly in comparison with active transport and intracellular binding mechanisms. These features include: linear accumulation at low concentrations; nonlinearity at higher concentrations; dependence on structural integrity of tissue; energy dependence and competition with other weak bases. Subcellular distribution studies have previously shown that weak bases accumulate extensively in membranes; however, the dependence of accumulation on the structural integrity of tissue suggests that this is not the only significant mechanism of accumulation. The results of a range of studies of tissue distribution of weak bases are discussed to illustrate that these findings are consistent with accumulation in lung and liver being attributable to a combination of lysosomal trapping and accumulation in membranes whereas, in muscle, accumulation in membranes is the predominant mechanism of accumulation. The possible pharmacokinetic significance of lysosomal trapping of weak bases is also discussed.</div></front></TEI><affiliations><list><country><li>Australie</li></country><region><li>Nouvelle-Galles du Sud</li></region><settlement><li>Sydney</li></settlement><orgName><li>Université de Sydney</li></orgName></list><tree><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Macintyre, Anna C" sort="Macintyre, Anna C" uniqKey="Macintyre A" first="Anna C." last="Macintyre">Anna C. Macintyre</name></region><name sortKey="Cutler, David J" sort="Cutler, David J" uniqKey="Cutler D" first="David J." last="Cutler">David J. Cutler</name><name sortKey="Cutler, David J" sort="Cutler, David J" uniqKey="Cutler D" first="David J." last="Cutler">David J. Cutler</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 003232 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 003232 | 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:BD4BBD782E017013EC5048D0744C4C0162F7AC94
|texte= The potential role of lysosomes in tissue distribution of weak bases
}}
| This area was generated with Dilib version V0.6.33. |  |