The contribution of lysosomal trapping in the uptake of desipramine and chloroquine by different tissues.
Identifieur interne : 001167 ( Ncbi/Merge ); précédent : 001166; suivant : 001168The contribution of lysosomal trapping in the uptake of desipramine and chloroquine by different tissues.
Auteurs : W A Daniel [Suisse] ; M H Bickel ; U E HoneggerSource :
- Pharmacology & toxicology [ 0901-9928 ] ; 1995.
Descripteurs français
- KwdFr :
- Animaux, Chloroquine (pharmacocinétique), Diazépam (pharmacocinétique), Désipramine (pharmacocinétique), Encéphale (métabolisme), Foie (métabolisme), Lysosomes (physiologie), Microtomie, Muscle diaphragme (métabolisme), Muscles squelettiques (métabolisme), Myocarde (métabolisme), Mâle, Poumon (métabolisme), Rat Sprague-Dawley, Rats, Rein (métabolisme), Répartition dans les tissus, Techniques in vitro, Thiopental (pharmacocinétique), Tissu adipeux (métabolisme).
- MESH :
- métabolisme : Encéphale, Foie, Muscle diaphragme, Muscles squelettiques, Myocarde, Poumon, Rein, Tissu adipeux.
- pharmacocinétique : Chloroquine, Diazépam, Désipramine, Thiopental.
- physiologie : Lysosomes.
- Animaux, Microtomie, Mâle, Rat Sprague-Dawley, Rats, Répartition dans les tissus, Techniques in vitro.
English descriptors
- KwdEn :
- Adipose Tissue (metabolism), Animals, Brain (metabolism), Chloroquine (pharmacokinetics), Desipramine (pharmacokinetics), Diaphragm (metabolism), Diazepam (pharmacokinetics), In Vitro Techniques, Kidney (metabolism), Liver (metabolism), Lung (metabolism), Lysosomes (physiology), Male, Microtomy, Muscle, Skeletal (metabolism), Myocardium (metabolism), Rats, Rats, Sprague-Dawley, Thiopental (pharmacokinetics), Tissue Distribution.
- MESH :
- chemical , pharmacokinetics : Chloroquine, Desipramine, Diazepam, Thiopental.
- metabolism : Adipose Tissue, Brain, Diaphragm, Kidney, Liver, Lung, Muscle, Skeletal, Myocardium.
- physiology : Lysosomes.
- Animals, In Vitro Techniques, Male, Microtomy, Rats, Rats, Sprague-Dawley, Tissue Distribution.
Abstract
Cationic amphiphilic drugs strongly accumulate in tissues of different organs. Uptake is controlled by two major mechanisms, non-specific binding to membrane phospholipids, and ion-trapping within acidic cellular compartments. The aim of this study was to assess the individual contributions of these two mechanisms on the uptake in vitro of desipramine and chloroquine into tissue slices of control and desipramine-treated rats. Drug uptake into intact slices was compared with uptake into slices with destroyed or non-functional acidic compartments. The sequence of desipramine uptake by tissue slices of eight different organs was: lungs > brain > heart > diaphragm > kidneys > skeletal muscles > adipose tissue > liver. The low desipramine concentration in liver may be due to metabolism of the parent drug by cytochrome P-450. Uptake of chloroquine differed widely between slices of different organs with the sequence: lungs > kidneys = brain = liver > diaphragm = heart = skeletal muscles > adipose tissue. Destruction or inactivation of the acidic compartments by homogenization and freeze-thawing or by ammonium chloride, sodium fluoride, or monensin, reduced drug uptake to similar extents. The reduction was organ-specific and may represent the size of the lysosomal compartment in the respective tissue cells. Uptake of chloroquine was more affected than that of desipramine, suggesting that ion-trapping is the main factor for chloroquine accumulation, while binding to membrane phospholipids, is the main factor for desipramine uptake. Single or multiple-dose treatments of rats with desipramine hardly had any effect on consecutive desipramine uptake into lung and liver slices, while the accumulation of chloroquine was enhanced in these slices. In conclusion, the extent of uptake of cationic amphiphilic drugs into tissue slices was tissue-specific, and the contribution of the two uptake mechanisms was strongly drug-dependent.
DOI: 10.1111/j.1600-0773.1995.tb01050.x
PubMed: 8835367
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first="W A" last="Daniel">W A Daniel</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pharmacology, University of Bern, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Pharmacology, University of Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region nuts="3" type="region">Canton de Berne</region></placeName><orgName type="university">Université de Berne</orgName></affiliation></author><author><name sortKey="Bickel, M H" sort="Bickel, M H" uniqKey="Bickel M" first="M H" last="Bickel">M H Bickel</name></author><author><name sortKey="Honegger, U E" sort="Honegger, U E" uniqKey="Honegger U" first="U E" last="Honegger">U E Honegger</name></author></analytic><series><title level="j">Pharmacology & toxicology</title><idno type="ISSN">0901-9928</idno><imprint><date when="1995" type="published">1995</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adipose Tissue (metabolism)</term><term>Animals</term><term>Brain (metabolism)</term><term>Chloroquine (pharmacokinetics)</term><term>Desipramine (pharmacokinetics)</term><term>Diaphragm (metabolism)</term><term>Diazepam (pharmacokinetics)</term><term>In Vitro Techniques</term><term>Kidney (metabolism)</term><term>Liver (metabolism)</term><term>Lung (metabolism)</term><term>Lysosomes (physiology)</term><term>Male</term><term>Microtomy</term><term>Muscle, Skeletal (metabolism)</term><term>Myocardium (metabolism)</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Thiopental (pharmacokinetics)</term><term>Tissue Distribution</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Chloroquine (pharmacocinétique)</term><term>Diazépam (pharmacocinétique)</term><term>Désipramine (pharmacocinétique)</term><term>Encéphale (métabolisme)</term><term>Foie (métabolisme)</term><term>Lysosomes (physiologie)</term><term>Microtomie</term><term>Muscle diaphragme (métabolisme)</term><term>Muscles squelettiques (métabolisme)</term><term>Myocarde (métabolisme)</term><term>Mâle</term><term>Poumon (métabolisme)</term><term>Rat Sprague-Dawley</term><term>Rats</term><term>Rein (métabolisme)</term><term>Répartition dans les tissus</term><term>Techniques in vitro</term><term>Thiopental (pharmacocinétique)</term><term>Tissu adipeux (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Chloroquine</term><term>Desipramine</term><term>Diazepam</term><term>Thiopental</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Adipose Tissue</term><term>Brain</term><term>Diaphragm</term><term>Kidney</term><term>Liver</term><term>Lung</term><term>Muscle, Skeletal</term><term>Myocardium</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Encéphale</term><term>Foie</term><term>Muscle diaphragme</term><term>Muscles squelettiques</term><term>Myocarde</term><term>Poumon</term><term>Rein</term><term>Tissu adipeux</term></keywords><keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Chloroquine</term><term>Diazépam</term><term>Désipramine</term><term>Thiopental</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Lysosomes</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Lysosomes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>In Vitro Techniques</term><term>Male</term><term>Microtomy</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Tissue Distribution</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Microtomie</term><term>Mâle</term><term>Rat Sprague-Dawley</term><term>Rats</term><term>Répartition dans les tissus</term><term>Techniques in vitro</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Cationic amphiphilic drugs strongly accumulate in tissues of different organs. Uptake is controlled by two major mechanisms, non-specific binding to membrane phospholipids, and ion-trapping within acidic cellular compartments. The aim of this study was to assess the individual contributions of these two mechanisms on the uptake in vitro of desipramine and chloroquine into tissue slices of control and desipramine-treated rats. Drug uptake into intact slices was compared with uptake into slices with destroyed or non-functional acidic compartments. The sequence of desipramine uptake by tissue slices of eight different organs was: lungs > brain > heart > diaphragm > kidneys > skeletal muscles > adipose tissue > liver. The low desipramine concentration in liver may be due to metabolism of the parent drug by cytochrome P-450. Uptake of chloroquine differed widely between slices of different organs with the sequence: lungs > kidneys = brain = liver > diaphragm = heart = skeletal muscles > adipose tissue. Destruction or inactivation of the acidic compartments by homogenization and freeze-thawing or by ammonium chloride, sodium fluoride, or monensin, reduced drug uptake to similar extents. The reduction was organ-specific and may represent the size of the lysosomal compartment in the respective tissue cells. Uptake of chloroquine was more affected than that of desipramine, suggesting that ion-trapping is the main factor for chloroquine accumulation, while binding to membrane phospholipids, is the main factor for desipramine uptake. Single or multiple-dose treatments of rats with desipramine hardly had any effect on consecutive desipramine uptake into lung and liver slices, while the accumulation of chloroquine was enhanced in these slices. In conclusion, the extent of uptake of cationic amphiphilic drugs into tissue slices was tissue-specific, and the contribution of the two uptake mechanisms was strongly drug-dependent.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">8835367</PMID><DateCompleted><Year>1997</Year><Month>01</Month><Day>24</Day></DateCompleted><DateRevised><Year>2019</Year><Month>09</Month><Day>05</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0901-9928</ISSN><JournalIssue CitedMedium="Print"><Volume>77</Volume><Issue>6</Issue><PubDate><Year>1995</Year><Month>Dec</Month></PubDate></JournalIssue><Title>Pharmacology & toxicology</Title><ISOAbbreviation>Pharmacol. Toxicol.</ISOAbbreviation></Journal><ArticleTitle>The contribution of lysosomal trapping in the uptake of desipramine and chloroquine by different tissues.</ArticleTitle><Pagination><MedlinePgn>402-6</MedlinePgn></Pagination><Abstract><AbstractText>Cationic amphiphilic drugs strongly accumulate in tissues of different organs. Uptake is controlled by two major mechanisms, non-specific binding to membrane phospholipids, and ion-trapping within acidic cellular compartments. The aim of this study was to assess the individual contributions of these two mechanisms on the uptake in vitro of desipramine and chloroquine into tissue slices of control and desipramine-treated rats. Drug uptake into intact slices was compared with uptake into slices with destroyed or non-functional acidic compartments. The sequence of desipramine uptake by tissue slices of eight different organs was: lungs > brain > heart > diaphragm > kidneys > skeletal muscles > adipose tissue > liver. The low desipramine concentration in liver may be due to metabolism of the parent drug by cytochrome P-450. Uptake of chloroquine differed widely between slices of different organs with the sequence: lungs > kidneys = brain = liver > diaphragm = heart = skeletal muscles > adipose tissue. Destruction or inactivation of the acidic compartments by homogenization and freeze-thawing or by ammonium chloride, sodium fluoride, or monensin, reduced drug uptake to similar extents. The reduction was organ-specific and may represent the size of the lysosomal compartment in the respective tissue cells. Uptake of chloroquine was more affected than that of desipramine, suggesting that ion-trapping is the main factor for chloroquine accumulation, while binding to membrane phospholipids, is the main factor for desipramine uptake. Single or multiple-dose treatments of rats with desipramine hardly had any effect on consecutive desipramine uptake into lung and liver slices, while the accumulation of chloroquine was enhanced in these slices. In conclusion, the extent of uptake of cationic amphiphilic drugs into tissue slices was tissue-specific, and the contribution of the two uptake mechanisms was strongly drug-dependent.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Daniel</LastName><ForeName>W A</ForeName><Initials>WA</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, University of Bern, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bickel</LastName><ForeName>M H</ForeName><Initials>MH</Initials></Author><Author ValidYN="Y"><LastName>Honegger</LastName><ForeName>U E</ForeName><Initials>UE</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Denmark</Country><MedlineTA>Pharmacol Toxicol</MedlineTA><NlmUniqueID>8702180</NlmUniqueID><ISSNLinking>0901-9928</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>886U3H6UFF</RegistryNumber><NameOfSubstance UI="D002738">Chloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>JI8Z5M7NA3</RegistryNumber><NameOfSubstance UI="D013874">Thiopental</NameOfSubstance></Chemical><Chemical><RegistryNumber>Q3JTX2Q7TU</RegistryNumber><NameOfSubstance UI="D003975">Diazepam</NameOfSubstance></Chemical><Chemical><RegistryNumber>TG537D343B</RegistryNumber><NameOfSubstance UI="D003891">Desipramine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000273" MajorTopicYN="N">Adipose Tissue</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002738" MajorTopicYN="N">Chloroquine</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003891" MajorTopicYN="N">Desipramine</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003964" MajorTopicYN="N">Diaphragm</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003975" MajorTopicYN="N">Diazepam</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D066298" MajorTopicYN="N">In Vitro Techniques</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007668" MajorTopicYN="N">Kidney</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008099" MajorTopicYN="N">Liver</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008168" MajorTopicYN="N">Lung</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008247" MajorTopicYN="N">Lysosomes</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008867" MajorTopicYN="N">Microtomy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018482" MajorTopicYN="N">Muscle, Skeletal</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009206" MajorTopicYN="N">Myocardium</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013874" MajorTopicYN="N">Thiopental</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014018" MajorTopicYN="N">Tissue Distribution</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1995</Year><Month>12</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1995</Year><Month>12</Month><Day>1</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1995</Year><Month>12</Month><Day>1</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">8835367</ArticleId><ArticleId IdType="doi">10.1111/j.1600-0773.1995.tb01050.x</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Suisse</li></country><region><li>Canton de Berne</li></region><settlement><li>Berne</li></settlement><orgName><li>Université de Berne</li></orgName></list><tree><noCountry><name sortKey="Bickel, M H" sort="Bickel, M H" uniqKey="Bickel M" first="M H" last="Bickel">M H Bickel</name><name sortKey="Honegger, U E" sort="Honegger, U E" uniqKey="Honegger U" first="U E" last="Honegger">U E Honegger</name></noCountry><country name="Suisse"><region name="Canton de Berne"><name sortKey="Daniel, W A" 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