Amitriptyline enhances extracellular tissue levels of adenosine in the rat hindpaw and inhibits adenosine uptake.
Identifieur interne : 000573 ( Ncbi/Merge ); précédent : 000572; suivant : 000574Amitriptyline enhances extracellular tissue levels of adenosine in the rat hindpaw and inhibits adenosine uptake.
Auteurs : Jana Sawynok [Canada] ; Allison R. Reid ; Xue Jun Liu ; Fiona E. ParkinsonSource :
- European journal of pharmacology [ 0014-2999 ] ; 2005.
English descriptors
- KwdEn :
- Adenosine (metabolism), Adenosine (pharmacokinetics), Adenosine (pharmacology), Adenosine Diphosphate (analogs & derivatives), Adenosine Diphosphate (pharmacology), Adenosine Monophosphate (pharmacology), Amitriptyline (pharmacology), Animals, Antidepressive Agents, Tricyclic (pharmacology), Biological Transport (drug effects), Capsaicin (pharmacology), Cell Line, Tumor, Dose-Response Relationship, Drug, Equilibrative-Nucleoside Transporter 2 (metabolism), Extracellular Space (drug effects), Extracellular Space (metabolism), Hindlimb (drug effects), Hindlimb (metabolism), Male, Microdialysis, Rats, Rats, Sprague-Dawley, Time Factors.
- MESH :
- chemical , analogs & derivatives : Adenosine Diphosphate.
- chemical , metabolism : Adenosine, Equilibrative-Nucleoside Transporter 2.
- chemical , pharmacokinetics : Adenosine.
- chemical , pharmacology : Adenosine, Adenosine Diphosphate, Adenosine Monophosphate, Amitriptyline, Antidepressive Agents, Tricyclic, Capsaicin.
- drug effects : Biological Transport, Extracellular Space, Hindlimb.
- metabolism : Extracellular Space, Hindlimb.
- Animals, Cell Line, Tumor, Dose-Response Relationship, Drug, Male, Microdialysis, Rats, Rats, Sprague-Dawley, Time Factors.
Abstract
Local administration of amitriptyline into the rat hindpaw produces peripheral antinociception; this is reduced by adenosine receptor antagonists and appears to involve endogenous adenosine. The present study used peripheral microdialysis: (a) to determine whether amitriptyline could enhance extracellular tissue levels of endogenous adenosine in the rat hindpaw and (b) to examine mechanisms by which such an increase could occur. Local injection of amitriptyline into the plantar hindpaw, at doses that produce peripheral antinociception (100-300 nmol), produced an increase in local extracellular levels of adenosine. When injected in combination with formalin, which also enhances such levels of adenosine, an additive increase was observed. This adenosine originated partly as nucleotide, as inhibition of ecto-5'-nucleotidase reduced the amount of adenosine detected in the probe following administration of amitriptyline. When administered in combination with exogenous adenosine, amitriptyline augmented recovery of adenosine in the probe. Pretreatment of rats with capsaicin augmented the ability of amitriptyline to increase adenosine levels detected in the dialysis probe; it also enhanced tissue recovery of exogenously administered adenosine. In uptake studies using cultured rat C6 glioma cells, amitriptyline inhibited adenosine uptake by an adenosine transporter (IC50 0.37 +/- 0.12 mM). In enzyme assays, amitriptyline had no effect on adenosine kinase or adenosine deaminase activity. These results demonstrate that amitriptyline: (a) enhances extracellular tissue levels of adenosine in the rat hindpaw following local administration in vivo and (b) inhibits adenosine uptake but has no effect on metabolism in vitro. Therefore, increased extracellular adenosine levels in vivo appear to result partially from extracellular conversion of nucleotide and partially from inhibition of uptake.
PubMed: 16156010
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 001240
- to stream PubMed, to step Curation: 001240
- to stream PubMed, to step Checkpoint: 001240
Links to Exploration step
pubmed:16156010Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Amitriptyline enhances extracellular tissue levels of adenosine in the rat hindpaw and inhibits adenosine uptake.</title><author><name sortKey="Sawynok, Jana" sort="Sawynok, Jana" uniqKey="Sawynok J" first="Jana" last="Sawynok">Jana Sawynok</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5. jana.sawynok@dal.ca</nlm:affiliation><country>Canada</country><wicri:regionArea>Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia</wicri:regionArea><wicri:noRegion>Nova Scotia</wicri:noRegion></affiliation></author><author><name sortKey="Reid, Allison R" sort="Reid, Allison R" uniqKey="Reid A" first="Allison R" last="Reid">Allison R. Reid</name></author><author><name sortKey="Liu, Xue Jun" sort="Liu, Xue Jun" uniqKey="Liu X" first="Xue Jun" last="Liu">Xue Jun Liu</name></author><author><name sortKey="Parkinson, Fiona E" sort="Parkinson, Fiona E" uniqKey="Parkinson F" first="Fiona E" last="Parkinson">Fiona E. Parkinson</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2005">2005</date><idno type="RBID">pubmed:16156010</idno><idno type="pmid">16156010</idno><idno type="wicri:Area/PubMed/Corpus">001240</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001240</idno><idno type="wicri:Area/PubMed/Curation">001240</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001240</idno><idno type="wicri:Area/PubMed/Checkpoint">001240</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001240</idno><idno type="wicri:Area/Ncbi/Merge">000573</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Amitriptyline enhances extracellular tissue levels of adenosine in the rat hindpaw and inhibits adenosine uptake.</title><author><name sortKey="Sawynok, Jana" sort="Sawynok, Jana" uniqKey="Sawynok J" first="Jana" last="Sawynok">Jana Sawynok</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5. jana.sawynok@dal.ca</nlm:affiliation><country>Canada</country><wicri:regionArea>Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia</wicri:regionArea><wicri:noRegion>Nova Scotia</wicri:noRegion></affiliation></author><author><name sortKey="Reid, Allison R" sort="Reid, Allison R" uniqKey="Reid A" first="Allison R" last="Reid">Allison R. Reid</name></author><author><name sortKey="Liu, Xue Jun" sort="Liu, Xue Jun" uniqKey="Liu X" first="Xue Jun" last="Liu">Xue Jun Liu</name></author><author><name sortKey="Parkinson, Fiona E" sort="Parkinson, Fiona E" uniqKey="Parkinson F" first="Fiona E" last="Parkinson">Fiona E. Parkinson</name></author></analytic><series><title level="j">European journal of pharmacology</title><idno type="ISSN">0014-2999</idno><imprint><date when="2005" type="published">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenosine (metabolism)</term><term>Adenosine (pharmacokinetics)</term><term>Adenosine (pharmacology)</term><term>Adenosine Diphosphate (analogs & derivatives)</term><term>Adenosine Diphosphate (pharmacology)</term><term>Adenosine Monophosphate (pharmacology)</term><term>Amitriptyline (pharmacology)</term><term>Animals</term><term>Antidepressive Agents, Tricyclic (pharmacology)</term><term>Biological Transport (drug effects)</term><term>Capsaicin (pharmacology)</term><term>Cell Line, Tumor</term><term>Dose-Response Relationship, Drug</term><term>Equilibrative-Nucleoside Transporter 2 (metabolism)</term><term>Extracellular Space (drug effects)</term><term>Extracellular Space (metabolism)</term><term>Hindlimb (drug effects)</term><term>Hindlimb (metabolism)</term><term>Male</term><term>Microdialysis</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Time Factors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Adenosine Diphosphate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adenosine</term><term>Equilibrative-Nucleoside Transporter 2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Adenosine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Adenosine</term><term>Adenosine Diphosphate</term><term>Adenosine Monophosphate</term><term>Amitriptyline</term><term>Antidepressive Agents, Tricyclic</term><term>Capsaicin</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Biological Transport</term><term>Extracellular Space</term><term>Hindlimb</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Extracellular Space</term><term>Hindlimb</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Dose-Response Relationship, Drug</term><term>Male</term><term>Microdialysis</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Time Factors</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Local administration of amitriptyline into the rat hindpaw produces peripheral antinociception; this is reduced by adenosine receptor antagonists and appears to involve endogenous adenosine. The present study used peripheral microdialysis: (a) to determine whether amitriptyline could enhance extracellular tissue levels of endogenous adenosine in the rat hindpaw and (b) to examine mechanisms by which such an increase could occur. Local injection of amitriptyline into the plantar hindpaw, at doses that produce peripheral antinociception (100-300 nmol), produced an increase in local extracellular levels of adenosine. When injected in combination with formalin, which also enhances such levels of adenosine, an additive increase was observed. This adenosine originated partly as nucleotide, as inhibition of ecto-5'-nucleotidase reduced the amount of adenosine detected in the probe following administration of amitriptyline. When administered in combination with exogenous adenosine, amitriptyline augmented recovery of adenosine in the probe. Pretreatment of rats with capsaicin augmented the ability of amitriptyline to increase adenosine levels detected in the dialysis probe; it also enhanced tissue recovery of exogenously administered adenosine. In uptake studies using cultured rat C6 glioma cells, amitriptyline inhibited adenosine uptake by an adenosine transporter (IC50 0.37 +/- 0.12 mM). In enzyme assays, amitriptyline had no effect on adenosine kinase or adenosine deaminase activity. These results demonstrate that amitriptyline: (a) enhances extracellular tissue levels of adenosine in the rat hindpaw following local administration in vivo and (b) inhibits adenosine uptake but has no effect on metabolism in vitro. Therefore, increased extracellular adenosine levels in vivo appear to result partially from extracellular conversion of nucleotide and partially from inhibition of uptake.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">16156010</PMID><DateCreated><Year>2005</Year><Month>09</Month><Day>09</Day></DateCreated><DateCompleted><Year>2005</Year><Month>09</Month><Day>23</Day></DateCompleted><DateRevised><Year>2016</Year><Month>11</Month><Day>24</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0014-2999</ISSN><JournalIssue CitedMedium="Print"><Volume>518</Volume><Issue>2-3</Issue><PubDate><Year>2005</Year><Month>Aug</Month><Day>22</Day></PubDate></JournalIssue><Title>European journal of pharmacology</Title><ISOAbbreviation>Eur. J. Pharmacol.</ISOAbbreviation></Journal><ArticleTitle>Amitriptyline enhances extracellular tissue levels of adenosine in the rat hindpaw and inhibits adenosine uptake.</ArticleTitle><Pagination><MedlinePgn>116-22</MedlinePgn></Pagination><Abstract><AbstractText>Local administration of amitriptyline into the rat hindpaw produces peripheral antinociception; this is reduced by adenosine receptor antagonists and appears to involve endogenous adenosine. The present study used peripheral microdialysis: (a) to determine whether amitriptyline could enhance extracellular tissue levels of endogenous adenosine in the rat hindpaw and (b) to examine mechanisms by which such an increase could occur. Local injection of amitriptyline into the plantar hindpaw, at doses that produce peripheral antinociception (100-300 nmol), produced an increase in local extracellular levels of adenosine. When injected in combination with formalin, which also enhances such levels of adenosine, an additive increase was observed. This adenosine originated partly as nucleotide, as inhibition of ecto-5'-nucleotidase reduced the amount of adenosine detected in the probe following administration of amitriptyline. When administered in combination with exogenous adenosine, amitriptyline augmented recovery of adenosine in the probe. Pretreatment of rats with capsaicin augmented the ability of amitriptyline to increase adenosine levels detected in the dialysis probe; it also enhanced tissue recovery of exogenously administered adenosine. In uptake studies using cultured rat C6 glioma cells, amitriptyline inhibited adenosine uptake by an adenosine transporter (IC50 0.37 +/- 0.12 mM). In enzyme assays, amitriptyline had no effect on adenosine kinase or adenosine deaminase activity. These results demonstrate that amitriptyline: (a) enhances extracellular tissue levels of adenosine in the rat hindpaw following local administration in vivo and (b) inhibits adenosine uptake but has no effect on metabolism in vitro. Therefore, increased extracellular adenosine levels in vivo appear to result partially from extracellular conversion of nucleotide and partially from inhibition of uptake.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sawynok</LastName><ForeName>Jana</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5. jana.sawynok@dal.ca</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Reid</LastName><ForeName>Allison R</ForeName><Initials>AR</Initials></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Xue Jun</ForeName><Initials>XJ</Initials></Author><Author ValidYN="Y"><LastName>Parkinson</LastName><ForeName>Fiona E</ForeName><Initials>FE</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Eur J Pharmacol</MedlineTA><NlmUniqueID>1254354</NlmUniqueID><ISSNLinking>0014-2999</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000929">Antidepressive Agents, Tricyclic</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D033722">Equilibrative-Nucleoside Transporter 2</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C438655">Slc29a2 protein, rat</NameOfSubstance></Chemical><Chemical><RegistryNumber>0T2A5439OE</RegistryNumber><NameOfSubstance UI="C008436">adenosine 5'-methylenediphosphate</NameOfSubstance></Chemical><Chemical><RegistryNumber>1806D8D52K</RegistryNumber><NameOfSubstance UI="D000639">Amitriptyline</NameOfSubstance></Chemical><Chemical><RegistryNumber>415SHH325A</RegistryNumber><NameOfSubstance UI="D000249">Adenosine Monophosphate</NameOfSubstance></Chemical><Chemical><RegistryNumber>61D2G4IYVH</RegistryNumber><NameOfSubstance UI="D000244">Adenosine Diphosphate</NameOfSubstance></Chemical><Chemical><RegistryNumber>K72T3FS567</RegistryNumber><NameOfSubstance UI="D000241">Adenosine</NameOfSubstance></Chemical><Chemical><RegistryNumber>S07O44R1ZM</RegistryNumber><NameOfSubstance UI="D002211">Capsaicin</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000241" MajorTopicYN="N">Adenosine</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000244" MajorTopicYN="N">Adenosine Diphosphate</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="N">analogs & derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000249" MajorTopicYN="N">Adenosine Monophosphate</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000639" MajorTopicYN="N">Amitriptyline</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000929" MajorTopicYN="N">Antidepressive Agents, Tricyclic</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001692" MajorTopicYN="N">Biological Transport</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002211" MajorTopicYN="N">Capsaicin</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D033722" MajorTopicYN="N">Equilibrative-Nucleoside Transporter 2</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005110" MajorTopicYN="N">Extracellular Space</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006614" MajorTopicYN="N">Hindlimb</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017551" MajorTopicYN="N">Microdialysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2005</Year><Month>9</Month><Day>13</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2005</Year><Month>9</Month><Day>24</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2005</Year><Month>9</Month><Day>13</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">16156010</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Liu, Xue Jun" sort="Liu, Xue Jun" uniqKey="Liu X" first="Xue Jun" last="Liu">Xue Jun Liu</name><name sortKey="Parkinson, Fiona E" sort="Parkinson, Fiona E" uniqKey="Parkinson F" first="Fiona E" last="Parkinson">Fiona E. Parkinson</name><name sortKey="Reid, Allison R" sort="Reid, Allison R" uniqKey="Reid A" first="Allison R" last="Reid">Allison R. Reid</name></noCountry><country name="Canada"><noRegion><name sortKey="Sawynok, Jana" sort="Sawynok, Jana" uniqKey="Sawynok J" first="Jana" last="Sawynok">Jana Sawynok</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000573 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 000573 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Ncbi
|étape= Merge
|type= RBID
|clé= pubmed:16156010
|texte= Amitriptyline enhances extracellular tissue levels of adenosine in the rat hindpaw and inhibits adenosine uptake.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:16156010" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonCanadaV1
| This area was generated with Dilib version V0.6.29. |  |