Interaction of 1-methyl-4-phenylpyridinium ion with human platelets
When uptake of the Parkinson's syndrome inducing neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and its major brain metabolite MPP + (1-methyl-4-phenylpyridinium ion) by human platelets were compared in platelet rich plasma, a much higher rate was observed for the metabolite. Th...
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| Veröffentlicht in: | Biochemical and biophysical research communications 1988-03, Vol.151 (2), p.897-904 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Buckman, Trent D. Chang, Ruth Sutphin, Mary S. Eiduson, Samuel |
| description | When uptake of the Parkinson's syndrome inducing neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and its major brain metabolite MPP
+ (1-methyl-4-phenylpyridinium ion) by human platelets were compared in platelet rich plasma, a much higher rate was observed for the metabolite. The uptake process was saturable (K
m
= 6.8 μM; V
max
= 0.064 nmole/min/mg protein) and could be blocked by inhibitors of serotonin uptake. The accumulation of MPP
+ by the platelets was accompanied by a decrease in intracellular ATP and an inhibition of mitochondrial state 3 respiration. These findings are consistent with earlier reports of the effect of MPP
+ on isolated mitochondria as a potential cytotoxic mechanism, but also demonstrate that the dopamine uptake system is not the only means by which this metabolite can be efficiently transported into cells. |
| doi_str_mv | 10.1016/S0006-291X(88)80366-8 |
| format | Article |
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+ (1-methyl-4-phenylpyridinium ion) by human platelets were compared in platelet rich plasma, a much higher rate was observed for the metabolite. The uptake process was saturable (K
m
= 6.8 μM; V
max
= 0.064 nmole/min/mg protein) and could be blocked by inhibitors of serotonin uptake. The accumulation of MPP
+ by the platelets was accompanied by a decrease in intracellular ATP and an inhibition of mitochondrial state 3 respiration. These findings are consistent with earlier reports of the effect of MPP
+ on isolated mitochondria as a potential cytotoxic mechanism, but also demonstrate that the dopamine uptake system is not the only means by which this metabolite can be efficiently transported into cells.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/S0006-291X(88)80366-8</identifier><identifier>PMID: 3258155</identifier><identifier>CODEN: BBRCA9</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; 1-Methyl-4-phenylpyridinium ; Adenosine Triphosphate - blood ; Biological and medical sciences ; Biological Transport ; Blood coagulation. Blood cells ; Blood Platelets - metabolism ; Fundamental and applied biological sciences. Psychology ; Humans ; Kinetics ; Molecular and cellular biology ; Neurotoxins - blood ; Platelet ; Pyridines - blood ; Pyridinium Compounds - blood ; Rotenone - pharmacology ; Serotonin Antagonists - pharmacology</subject><ispartof>Biochemical and biophysical research communications, 1988-03, Vol.151 (2), p.897-904</ispartof><rights>1988 Academic Press, Inc.</rights><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-273c3d0c58b44ce33d21e8ee340e677476748011044e9c46d75745edfeeeabd43</citedby><cites>FETCH-LOGICAL-c421t-273c3d0c58b44ce33d21e8ee340e677476748011044e9c46d75745edfeeeabd43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0006-291X(88)80366-8$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19557584$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3258155$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Buckman, Trent D.</creatorcontrib><creatorcontrib>Chang, Ruth</creatorcontrib><creatorcontrib>Sutphin, Mary S.</creatorcontrib><creatorcontrib>Eiduson, Samuel</creatorcontrib><title>Interaction of 1-methyl-4-phenylpyridinium ion with human platelets</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>When uptake of the Parkinson's syndrome inducing neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and its major brain metabolite MPP
+ (1-methyl-4-phenylpyridinium ion) by human platelets were compared in platelet rich plasma, a much higher rate was observed for the metabolite. The uptake process was saturable (K
m
= 6.8 μM; V
max
= 0.064 nmole/min/mg protein) and could be blocked by inhibitors of serotonin uptake. The accumulation of MPP
+ by the platelets was accompanied by a decrease in intracellular ATP and an inhibition of mitochondrial state 3 respiration. These findings are consistent with earlier reports of the effect of MPP
+ on isolated mitochondria as a potential cytotoxic mechanism, but also demonstrate that the dopamine uptake system is not the only means by which this metabolite can be efficiently transported into cells.</description><subject>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</subject><subject>1-Methyl-4-phenylpyridinium</subject><subject>Adenosine Triphosphate - blood</subject><subject>Biological and medical sciences</subject><subject>Biological Transport</subject><subject>Blood coagulation. Blood cells</subject><subject>Blood Platelets - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Molecular and cellular biology</subject><subject>Neurotoxins - blood</subject><subject>Platelet</subject><subject>Pyridines - blood</subject><subject>Pyridinium Compounds - blood</subject><subject>Rotenone - pharmacology</subject><subject>Serotonin Antagonists - pharmacology</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1988</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMlKBDEQhoMo47g8gtAXRQ_RpJN00ieRwQ0EDyp4C5mkmon0ZpJW5u3tWdCjpzrUV1V_fQidUHJJCS2uXgghBc5L-n6u1IUirCiw2kFTSkqCc0r4Lpr-IvvoIMYPQijlRTlBE5YLRYWYotljmyAYm3zXZl2VUdxAWixrzHG_gHZZ98vgnW_90GQr5NunRbYYGtNmfW0S1JDiEdqrTB3heFsP0dvd7evsAT893z_Obp6w5TlNOJfMMkesUHPOLTDmcgoKgHEChZRcFpKrMSHhHErLCyeF5AJcBQBm7jg7RGebvX3oPgeISTc-Wqhr00I3RD0-pHJWyhEUG9CGLsYAle6Db0xYakr0Sp5ey9MrM1opvZan1Th3sj0wzBtwv1NbW2P_dNs30Zq6Cqa1Pv4tL4WQQq2CXm84GG18eQg6Wg-tBecD2KRd5_9J8gNEuIt7</recordid><startdate>19880315</startdate><enddate>19880315</enddate><creator>Buckman, Trent D.</creator><creator>Chang, Ruth</creator><creator>Sutphin, Mary S.</creator><creator>Eiduson, Samuel</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>19880315</creationdate><title>Interaction of 1-methyl-4-phenylpyridinium ion with human platelets</title><author>Buckman, Trent D. ; Chang, Ruth ; Sutphin, Mary S. ; Eiduson, Samuel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-273c3d0c58b44ce33d21e8ee340e677476748011044e9c46d75745edfeeeabd43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1988</creationdate><topic>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</topic><topic>1-Methyl-4-phenylpyridinium</topic><topic>Adenosine Triphosphate - blood</topic><topic>Biological and medical sciences</topic><topic>Biological Transport</topic><topic>Blood coagulation. Blood cells</topic><topic>Blood Platelets - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Molecular and cellular biology</topic><topic>Neurotoxins - blood</topic><topic>Platelet</topic><topic>Pyridines - blood</topic><topic>Pyridinium Compounds - blood</topic><topic>Rotenone - pharmacology</topic><topic>Serotonin Antagonists - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Buckman, Trent D.</creatorcontrib><creatorcontrib>Chang, Ruth</creatorcontrib><creatorcontrib>Sutphin, Mary S.</creatorcontrib><creatorcontrib>Eiduson, Samuel</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Buckman, Trent D.</au><au>Chang, Ruth</au><au>Sutphin, Mary S.</au><au>Eiduson, Samuel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interaction of 1-methyl-4-phenylpyridinium ion with human platelets</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>1988-03-15</date><risdate>1988</risdate><volume>151</volume><issue>2</issue><spage>897</spage><epage>904</epage><pages>897-904</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><coden>BBRCA9</coden><abstract>When uptake of the Parkinson's syndrome inducing neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and its major brain metabolite MPP
+ (1-methyl-4-phenylpyridinium ion) by human platelets were compared in platelet rich plasma, a much higher rate was observed for the metabolite. The uptake process was saturable (K
m
= 6.8 μM; V
max
= 0.064 nmole/min/mg protein) and could be blocked by inhibitors of serotonin uptake. The accumulation of MPP
+ by the platelets was accompanied by a decrease in intracellular ATP and an inhibition of mitochondrial state 3 respiration. These findings are consistent with earlier reports of the effect of MPP
+ on isolated mitochondria as a potential cytotoxic mechanism, but also demonstrate that the dopamine uptake system is not the only means by which this metabolite can be efficiently transported into cells.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>3258155</pmid><doi>10.1016/S0006-291X(88)80366-8</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Biochemical and biophysical research communications, 1988-03, Vol.151 (2), p.897-904 |
| issn | 0006-291X 1090-2104 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine 1-Methyl-4-phenylpyridinium Adenosine Triphosphate - blood Biological and medical sciences Biological Transport Blood coagulation. Blood cells Blood Platelets - metabolism Fundamental and applied biological sciences. Psychology Humans Kinetics Molecular and cellular biology Neurotoxins - blood Platelet Pyridines - blood Pyridinium Compounds - blood Rotenone - pharmacology Serotonin Antagonists - pharmacology |
| title | Interaction of 1-methyl-4-phenylpyridinium ion with human platelets |
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