Up-regulation of carnitine transporters helps maintain tissue carnitine levels in carnitine deficiency induced by pivalic acid
Pivalic acid (PVA) forms conjugates with endogenous carnitine and enhances its excretion. The purpose of this study is to determine whether tissue carnitine levels decrease in parallel with plasma levels in carnitine deficiency induced by PVA. PVA was orally administered to rats for 5 days. Carnitin...
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| Veröffentlicht in: | Pharmaceutical research 2001-04, Vol.18 (4), p.439-445 |
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| creator | OKUDAIRA, Noriko FUJIGAKI, Masao NAKAYOSHI, Takemi KOMIYA, Izumi SUGIYAMA, Yuichi |
| description | Pivalic acid (PVA) forms conjugates with endogenous carnitine and enhances its excretion. The purpose of this study is to determine whether tissue carnitine levels decrease in parallel with plasma levels in carnitine deficiency induced by PVA.
PVA was orally administered to rats for 5 days. Carnitine levels in plasma, liver, kidney, muscle, and heart were monitored. The tissue uptake clearance (CLuptake) was determined in vivo by the integration plot method. Hepatocytes were prepared from control and PVA-treated rats, and the uptake of L-carnitine was determined.
Plasma concentrations of L-carnitine decreased as a result of the enhanced carnitine elimination as pivaloylcarnitine (PCN) when rats were treated with PVA. However, L-carnitine concentrations in liver, muscle, and heart remained relatively constant during the study. period. CLuptake increased in liver and muscle and, thus, the rate of carnitine uptake from plasma into these tissues did not change even at low plasma concentrations. This helps maintain carnitine levels in these tissues. Up-regulation of carnitine transporters is suggested to be a mechanism for the increased CLuptake.
In the carnitine deficiency state induced by PVA, increased CLuptake owing to up-regulation of carnitine transporters is suggested to help maintain carnitine levels in some tissues. |
| doi_str_mv | 10.1023/a:1011042008169 |
| format | Article |
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PVA was orally administered to rats for 5 days. Carnitine levels in plasma, liver, kidney, muscle, and heart were monitored. The tissue uptake clearance (CLuptake) was determined in vivo by the integration plot method. Hepatocytes were prepared from control and PVA-treated rats, and the uptake of L-carnitine was determined.
Plasma concentrations of L-carnitine decreased as a result of the enhanced carnitine elimination as pivaloylcarnitine (PCN) when rats were treated with PVA. However, L-carnitine concentrations in liver, muscle, and heart remained relatively constant during the study. period. CLuptake increased in liver and muscle and, thus, the rate of carnitine uptake from plasma into these tissues did not change even at low plasma concentrations. This helps maintain carnitine levels in these tissues. Up-regulation of carnitine transporters is suggested to be a mechanism for the increased CLuptake.
In the carnitine deficiency state induced by PVA, increased CLuptake owing to up-regulation of carnitine transporters is suggested to help maintain carnitine levels in some tissues.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1023/a:1011042008169</identifier><identifier>PMID: 11451029</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Animals ; Biological and medical sciences ; Carnitine - analogs & derivatives ; Carnitine - deficiency ; Carnitine - metabolism ; Carrier Proteins - biosynthesis ; Drug dosages ; General and cellular metabolism. Vitamins ; Heart ; Injections, Intra-Arterial ; Injections, Intravenous ; Laboratory animals ; Liver ; Male ; Medical sciences ; Organic Cation Transport Proteins ; Pentanoic Acids - administration & dosage ; Pentanoic Acids - pharmacology ; Pharmaceuticals ; Pharmacology. Drug treatments ; Plasma ; Rats ; Rats, Sprague-Dawley ; Solute Carrier Family 22 Member 5 ; Tissue Distribution - drug effects ; Tissue Distribution - physiology ; Up-Regulation - drug effects ; Up-Regulation - physiology ; Urine</subject><ispartof>Pharmaceutical research, 2001-04, Vol.18 (4), p.439-445</ispartof><rights>2001 INIST-CNRS</rights><rights>Copyright Kluwer Academic Publishers Apr 2001</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-de4fc4766503b9cc75c51e98d9b195e2a62fd2372fa4e82ffa950d87cf4090303</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1062843$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11451029$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>OKUDAIRA, Noriko</creatorcontrib><creatorcontrib>FUJIGAKI, Masao</creatorcontrib><creatorcontrib>NAKAYOSHI, Takemi</creatorcontrib><creatorcontrib>KOMIYA, Izumi</creatorcontrib><creatorcontrib>SUGIYAMA, Yuichi</creatorcontrib><title>Up-regulation of carnitine transporters helps maintain tissue carnitine levels in carnitine deficiency induced by pivalic acid</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>Pivalic acid (PVA) forms conjugates with endogenous carnitine and enhances its excretion. The purpose of this study is to determine whether tissue carnitine levels decrease in parallel with plasma levels in carnitine deficiency induced by PVA.
PVA was orally administered to rats for 5 days. Carnitine levels in plasma, liver, kidney, muscle, and heart were monitored. The tissue uptake clearance (CLuptake) was determined in vivo by the integration plot method. Hepatocytes were prepared from control and PVA-treated rats, and the uptake of L-carnitine was determined.
Plasma concentrations of L-carnitine decreased as a result of the enhanced carnitine elimination as pivaloylcarnitine (PCN) when rats were treated with PVA. However, L-carnitine concentrations in liver, muscle, and heart remained relatively constant during the study. period. CLuptake increased in liver and muscle and, thus, the rate of carnitine uptake from plasma into these tissues did not change even at low plasma concentrations. This helps maintain carnitine levels in these tissues. Up-regulation of carnitine transporters is suggested to be a mechanism for the increased CLuptake.
In the carnitine deficiency state induced by PVA, increased CLuptake owing to up-regulation of carnitine transporters is suggested to help maintain carnitine levels in some tissues.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Carnitine - analogs & derivatives</subject><subject>Carnitine - deficiency</subject><subject>Carnitine - metabolism</subject><subject>Carrier Proteins - biosynthesis</subject><subject>Drug dosages</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Heart</subject><subject>Injections, Intra-Arterial</subject><subject>Injections, Intravenous</subject><subject>Laboratory animals</subject><subject>Liver</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Organic Cation Transport Proteins</subject><subject>Pentanoic Acids - administration & dosage</subject><subject>Pentanoic Acids - pharmacology</subject><subject>Pharmaceuticals</subject><subject>Pharmacology. Drug treatments</subject><subject>Plasma</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Solute Carrier Family 22 Member 5</subject><subject>Tissue Distribution - drug effects</subject><subject>Tissue Distribution - physiology</subject><subject>Up-Regulation - drug effects</subject><subject>Up-Regulation - physiology</subject><subject>Urine</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpd0M1LHTEQAPAglfrUnnsroYi3tZOvzaa3In6B4EXB25KXTGwkb3eb7Arv0r-9KX1F8TAMzPxmGIaQzwzOGHDxzX5nwBhIDtCx1uyRFVNaNAbk4weyAs1l02nJDshhKc_wFxn5kRwwJlWdNyvy-2FqMj4tyc5xHOgYqLN5iHMckM7ZDmUa84y50J-YpkI3Ng5zDTrHUhZ8gxO-YCq0tl5rHkN0EQe3rXW_OPR0vaVTfLEpOmpd9MdkP9hU8NMuH5GHy4v78-vm9u7q5vzHbeOEVnPjUQYnddsqEGvjnFZOMTSdN2tmFHLb8uC50DxYiR0PwRoFvtMuSDAgQByR0397pzz-WrDM_SYWhynZAcel9JoB8K5TFX59B5_HJQ_1tp5zrkFo2Vb0ZYeW9QZ9P-W4sXnb_39rBSc7YIuzKdRHulheHbS8k0L8AahmiGU</recordid><startdate>20010401</startdate><enddate>20010401</enddate><creator>OKUDAIRA, Noriko</creator><creator>FUJIGAKI, Masao</creator><creator>NAKAYOSHI, Takemi</creator><creator>KOMIYA, Izumi</creator><creator>SUGIYAMA, Yuichi</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20010401</creationdate><title>Up-regulation of carnitine transporters helps maintain tissue carnitine levels in carnitine deficiency induced by pivalic acid</title><author>OKUDAIRA, Noriko ; FUJIGAKI, Masao ; NAKAYOSHI, Takemi ; KOMIYA, Izumi ; SUGIYAMA, Yuichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-de4fc4766503b9cc75c51e98d9b195e2a62fd2372fa4e82ffa950d87cf4090303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Carnitine - analogs & derivatives</topic><topic>Carnitine - deficiency</topic><topic>Carnitine - metabolism</topic><topic>Carrier Proteins - biosynthesis</topic><topic>Drug dosages</topic><topic>General and cellular metabolism. Vitamins</topic><topic>Heart</topic><topic>Injections, Intra-Arterial</topic><topic>Injections, Intravenous</topic><topic>Laboratory animals</topic><topic>Liver</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Organic Cation Transport Proteins</topic><topic>Pentanoic Acids - administration & dosage</topic><topic>Pentanoic Acids - pharmacology</topic><topic>Pharmaceuticals</topic><topic>Pharmacology. Drug treatments</topic><topic>Plasma</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Solute Carrier Family 22 Member 5</topic><topic>Tissue Distribution - drug effects</topic><topic>Tissue Distribution - physiology</topic><topic>Up-Regulation - drug effects</topic><topic>Up-Regulation - physiology</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>OKUDAIRA, Noriko</creatorcontrib><creatorcontrib>FUJIGAKI, Masao</creatorcontrib><creatorcontrib>NAKAYOSHI, Takemi</creatorcontrib><creatorcontrib>KOMIYA, Izumi</creatorcontrib><creatorcontrib>SUGIYAMA, Yuichi</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>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>OKUDAIRA, Noriko</au><au>FUJIGAKI, Masao</au><au>NAKAYOSHI, Takemi</au><au>KOMIYA, Izumi</au><au>SUGIYAMA, Yuichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Up-regulation of carnitine transporters helps maintain tissue carnitine levels in carnitine deficiency induced by pivalic acid</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>2001-04-01</date><risdate>2001</risdate><volume>18</volume><issue>4</issue><spage>439</spage><epage>445</epage><pages>439-445</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>Pivalic acid (PVA) forms conjugates with endogenous carnitine and enhances its excretion. The purpose of this study is to determine whether tissue carnitine levels decrease in parallel with plasma levels in carnitine deficiency induced by PVA.
PVA was orally administered to rats for 5 days. Carnitine levels in plasma, liver, kidney, muscle, and heart were monitored. The tissue uptake clearance (CLuptake) was determined in vivo by the integration plot method. Hepatocytes were prepared from control and PVA-treated rats, and the uptake of L-carnitine was determined.
Plasma concentrations of L-carnitine decreased as a result of the enhanced carnitine elimination as pivaloylcarnitine (PCN) when rats were treated with PVA. However, L-carnitine concentrations in liver, muscle, and heart remained relatively constant during the study. period. CLuptake increased in liver and muscle and, thus, the rate of carnitine uptake from plasma into these tissues did not change even at low plasma concentrations. This helps maintain carnitine levels in these tissues. Up-regulation of carnitine transporters is suggested to be a mechanism for the increased CLuptake.
In the carnitine deficiency state induced by PVA, increased CLuptake owing to up-regulation of carnitine transporters is suggested to help maintain carnitine levels in some tissues.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>11451029</pmid><doi>10.1023/a:1011042008169</doi><tpages>7</tpages></addata></record> |
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| ispartof | Pharmaceutical research, 2001-04, Vol.18 (4), p.439-445 |
| issn | 0724-8741 1573-904X |
| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Animals Biological and medical sciences Carnitine - analogs & derivatives Carnitine - deficiency Carnitine - metabolism Carrier Proteins - biosynthesis Drug dosages General and cellular metabolism. Vitamins Heart Injections, Intra-Arterial Injections, Intravenous Laboratory animals Liver Male Medical sciences Organic Cation Transport Proteins Pentanoic Acids - administration & dosage Pentanoic Acids - pharmacology Pharmaceuticals Pharmacology. Drug treatments Plasma Rats Rats, Sprague-Dawley Solute Carrier Family 22 Member 5 Tissue Distribution - drug effects Tissue Distribution - physiology Up-Regulation - drug effects Up-Regulation - physiology Urine |
| title | Up-regulation of carnitine transporters helps maintain tissue carnitine levels in carnitine deficiency induced by pivalic acid |
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