Adenosine A1 and A2A receptors and nitrobenzylthioinosine-sensitive transporters in gerbil brain: no changes following long-term treatment with the adenosine transport inhibitor propentofylline.
Identifieur interne : 001902 ( PubMed/Corpus ); précédent : 001901; suivant : 001903Adenosine A1 and A2A receptors and nitrobenzylthioinosine-sensitive transporters in gerbil brain: no changes following long-term treatment with the adenosine transport inhibitor propentofylline.
Auteurs : F E Parkinson ; B. Johansson ; K. Lindström ; B B FredholmSource :
- Neuropharmacology [ 0028-3908 ] ; 1996.
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Adenosine, Receptors, Purinergic P1.
- chemical , pharmacology : Anti-Ulcer Agents, Guanosine Triphosphate, Xanthines.
- metabolism : Brain.
- Animals, Autoradiography, Binding, Competitive, Gerbillinae, In Situ Hybridization.
Abstract
There is evidence that adenosine is an endogenous neuroprotective substance in the gerbil and that propentofylline, a novel xanthine derivative that acts as a transport inhibitor, exerts part of its neuroprotective activity in this species by enhancing adenosine actions. Using autoradiography we have examined the distribution of adenosine A1 and A2A receptors and of equilibrative adenosine transporters in gerbil brain as well as the possible changes induced by repeated treatment with propentofylline. Nucleoside transporters, studied by [3H]NBMPR binding, were found to be widely distributed in the gerbil brain, with no clear relationship to the distribution of adenosine receptors. Adenosine A2A receptors, studied by [3H]CGS 21680 binding and by in situ hybridization, were found to be present in intrinsic neurons in the caudate putamen, nucleus accumbens and tuberculum olfactorium. Adenosine A1 receptors were studied by examining the binding of [3H]CHA, an agonist, and [3H]DPCPX, an antagonist. There was an overall similarity in the distribution of binding sites for these two ligands, and a similarity with the distribution in the rat. However, the antagonist was found to label certain structures, especially white matter structures, more than the agonist. It is argued that these binding sites for antagonists represent receptors that are in transit from the site of synthesis in the perikaryon to the destination in the nerve terminal, and are not coupled to G proteins. There were no differences in the binding of any of these ligands or in A2A mRNA following 2 weeks' treatment with propentofylline, indicating that the drug has minimal effects on adenosine mechanisms under basal physiological conditions. This also suggests that tolerance to adenosine-related effects of the drug is less likely to occur.
PubMed: 8684600
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Lindström</name></author><author><name sortKey="Fredholm, B B" sort="Fredholm, B B" uniqKey="Fredholm B" first="B B" last="Fredholm">B B Fredholm</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1996">1996</date><idno type="RBID">pubmed:8684600</idno><idno type="pmid">8684600</idno><idno type="wicri:Area/PubMed/Corpus">001902</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001902</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Adenosine A1 and A2A receptors and nitrobenzylthioinosine-sensitive transporters in gerbil brain: no changes following long-term treatment with the adenosine transport inhibitor propentofylline.</title><author><name sortKey="Parkinson, F E" sort="Parkinson, F E" uniqKey="Parkinson F" first="F E" last="Parkinson">F E Parkinson</name><affiliation><nlm:affiliation>Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Johansson, B" sort="Johansson, B" uniqKey="Johansson B" first="B" last="Johansson">B. Johansson</name></author><author><name sortKey="Lindstrom, K" sort="Lindstrom, K" uniqKey="Lindstrom K" first="K" last="Lindström">K. Lindström</name></author><author><name sortKey="Fredholm, B B" sort="Fredholm, B B" uniqKey="Fredholm B" first="B B" last="Fredholm">B B Fredholm</name></author></analytic><series><title level="j">Neuropharmacology</title><idno type="ISSN">0028-3908</idno><imprint><date when="1996" type="published">1996</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenosine (metabolism)</term><term>Animals</term><term>Anti-Ulcer Agents (pharmacology)</term><term>Autoradiography</term><term>Binding, Competitive</term><term>Brain (metabolism)</term><term>Gerbillinae</term><term>Guanosine Triphosphate (pharmacology)</term><term>In Situ Hybridization</term><term>Receptors, Purinergic P1 (metabolism)</term><term>Xanthines (pharmacology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adenosine</term><term>Receptors, Purinergic P1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-Ulcer Agents</term><term>Guanosine Triphosphate</term><term>Xanthines</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Autoradiography</term><term>Binding, Competitive</term><term>Gerbillinae</term><term>In Situ Hybridization</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">There is evidence that adenosine is an endogenous neuroprotective substance in the gerbil and that propentofylline, a novel xanthine derivative that acts as a transport inhibitor, exerts part of its neuroprotective activity in this species by enhancing adenosine actions. Using autoradiography we have examined the distribution of adenosine A1 and A2A receptors and of equilibrative adenosine transporters in gerbil brain as well as the possible changes induced by repeated treatment with propentofylline. Nucleoside transporters, studied by [3H]NBMPR binding, were found to be widely distributed in the gerbil brain, with no clear relationship to the distribution of adenosine receptors. Adenosine A2A receptors, studied by [3H]CGS 21680 binding and by in situ hybridization, were found to be present in intrinsic neurons in the caudate putamen, nucleus accumbens and tuberculum olfactorium. Adenosine A1 receptors were studied by examining the binding of [3H]CHA, an agonist, and [3H]DPCPX, an antagonist. There was an overall similarity in the distribution of binding sites for these two ligands, and a similarity with the distribution in the rat. However, the antagonist was found to label certain structures, especially white matter structures, more than the agonist. It is argued that these binding sites for antagonists represent receptors that are in transit from the site of synthesis in the perikaryon to the destination in the nerve terminal, and are not coupled to G proteins. There were no differences in the binding of any of these ligands or in A2A mRNA following 2 weeks' treatment with propentofylline, indicating that the drug has minimal effects on adenosine mechanisms under basal physiological conditions. This also suggests that tolerance to adenosine-related effects of the drug is less likely to occur.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">8684600</PMID><DateCreated><Year>1996</Year><Month>08</Month><Day>19</Day></DateCreated><DateCompleted><Year>1996</Year><Month>08</Month><Day>19</Day></DateCompleted><DateRevised><Year>2014</Year><Month>11</Month><Day>20</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0028-3908</ISSN><JournalIssue CitedMedium="Print"><Volume>35</Volume><Issue>1</Issue><PubDate><Year>1996</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Neuropharmacology</Title><ISOAbbreviation>Neuropharmacology</ISOAbbreviation></Journal><ArticleTitle>Adenosine A1 and A2A receptors and nitrobenzylthioinosine-sensitive transporters in gerbil brain: no changes following long-term treatment with the adenosine transport inhibitor propentofylline.</ArticleTitle><Pagination><MedlinePgn>79-89</MedlinePgn></Pagination><Abstract><AbstractText>There is evidence that adenosine is an endogenous neuroprotective substance in the gerbil and that propentofylline, a novel xanthine derivative that acts as a transport inhibitor, exerts part of its neuroprotective activity in this species by enhancing adenosine actions. Using autoradiography we have examined the distribution of adenosine A1 and A2A receptors and of equilibrative adenosine transporters in gerbil brain as well as the possible changes induced by repeated treatment with propentofylline. Nucleoside transporters, studied by [3H]NBMPR binding, were found to be widely distributed in the gerbil brain, with no clear relationship to the distribution of adenosine receptors. Adenosine A2A receptors, studied by [3H]CGS 21680 binding and by in situ hybridization, were found to be present in intrinsic neurons in the caudate putamen, nucleus accumbens and tuberculum olfactorium. Adenosine A1 receptors were studied by examining the binding of [3H]CHA, an agonist, and [3H]DPCPX, an antagonist. There was an overall similarity in the distribution of binding sites for these two ligands, and a similarity with the distribution in the rat. However, the antagonist was found to label certain structures, especially white matter structures, more than the agonist. It is argued that these binding sites for antagonists represent receptors that are in transit from the site of synthesis in the perikaryon to the destination in the nerve terminal, and are not coupled to G proteins. There were no differences in the binding of any of these ligands or in A2A mRNA following 2 weeks' treatment with propentofylline, indicating that the drug has minimal effects on adenosine mechanisms under basal physiological conditions. This also suggests that tolerance to adenosine-related effects of the drug is less likely to occur.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Parkinson</LastName><ForeName>F E</ForeName><Initials>FE</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Johansson</LastName><ForeName>B</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Lindström</LastName><ForeName>K</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Fredholm</LastName><ForeName>B B</ForeName><Initials>BB</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Neuropharmacology</MedlineTA><NlmUniqueID>0236217</NlmUniqueID><ISSNLinking>0028-3908</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000897">Anti-Ulcer Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018047">Receptors, Purinergic P1</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014970">Xanthines</NameOfSubstance></Chemical><Chemical><RegistryNumber>5RTA398U4H</RegistryNumber><NameOfSubstance UI="C032114">propentofylline</NameOfSubstance></Chemical><Chemical><RegistryNumber>86-01-1</RegistryNumber><NameOfSubstance UI="D006160">Guanosine Triphosphate</NameOfSubstance></Chemical><Chemical><RegistryNumber>K72T3FS567</RegistryNumber><NameOfSubstance UI="D000241">Adenosine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000241" MajorTopicYN="N">Adenosine</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000897" MajorTopicYN="N">Anti-Ulcer Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001345" MajorTopicYN="N">Autoradiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001667" MajorTopicYN="N">Binding, Competitive</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005849" MajorTopicYN="N">Gerbillinae</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006160" MajorTopicYN="N">Guanosine Triphosphate</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017403" MajorTopicYN="N">In Situ Hybridization</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018047" MajorTopicYN="N">Receptors, Purinergic P1</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014970" MajorTopicYN="N">Xanthines</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1996</Year><Month>1</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1996</Year><Month>1</Month><Day>1</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1996</Year><Month>1</Month><Day>1</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">8684600</ArticleId><ArticleId IdType="pii">0028390895001557</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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