beta-Adrenergics enhance brain extraction of levodopa.
Identifieur interne : 006098 ( Main/Merge ); précédent : 006097; suivant : 006099beta-Adrenergics enhance brain extraction of levodopa.
Auteurs : Ergun Y. Uc [États-Unis] ; Gerald A. Dienel ; Nancy F. Cruz ; Sami I. HarikSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2002.
English descriptors
- KwdEn :
- Adrenergic beta-Agonists (pharmacology), Adrenergic beta-Antagonists (pharmacology), Animals, Antiparkinson Agents (metabolism), Antiparkinson Agents (therapeutic use), Blood-Brain Barrier (drug effects), Brain (blood supply), Brain (drug effects), Cerebrovascular Circulation (physiology), Levodopa (metabolism), Levodopa (therapeutic use), Male, Parkinson Disease (drug therapy), Rats, Rats, Wistar.
- MESH :
- chemical , metabolism : Antiparkinson Agents, Levodopa.
- chemical , pharmacology : Adrenergic beta-Agonists, Adrenergic beta-Antagonists.
- chemical , therapeutic use : Antiparkinson Agents, Levodopa.
- blood supply : Brain.
- drug effects : Blood-Brain Barrier, Brain.
- drug therapy : Parkinson Disease.
- physiology : Cerebrovascular Circulation.
- Animals, Male, Rats, Rats, Wistar.
Abstract
We sought to determine whether beta-adrenergic agonists enhance the brain extraction of L-dopa and L-leucine. Systemic administration of beta-adrenergic agonists increase brain concentrations of L-dopa and other large neutral amino acids (LNAA) in rats and monkeys and may improve symptoms and reduce daily L-dopa requirement in patients with Parkinson's disease. Cerebral blood flow (CBF) using [3H]nicotine and the extraction fraction of 14C-labeled L-dopa or L-leucine were measured simultaneously in various brain regions of conscious rats using the dual-isotope indicator fractionation technique after intraperitoneal administration of isoproterenol (a peripheral nonselective beta-adrenergic agonist), or clenbuterol (a beta2-adrenergic agonist that crosses the blood-brain barrier), or beta-adrenergic agonist preceded by nadolol (a peripheral nonselective beta-adrenergic antagonist), or saline vehicle. Both beta-adrenergic agonists increased regional brain extraction fraction of L-dopa and L-leucine tracers by 35-45%, without altering regional CBF. These changes were accompanied by about a 30% decrease in plasma branched chain LNAA concentrations. Nadolol blocked all these effects. beta-Adrenergic agonists increase the brain extraction of L-dopa and leucine, mainly by peripheral mechanisms that reduce the levels of other competing plasma LNAAs for transport. Thus, beta-adrenergic agonists might be useful in the treatment of patients with Parkinson's disease by enhancing delivery of L-dopa to the brain.
PubMed: 11835439
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">beta-Adrenergics enhance brain extraction of levodopa.</title><author><name sortKey="Uc, Ergun Y" sort="Uc, Ergun Y" uniqKey="Uc E" first="Ergun Y" last="Uc">Ergun Y. Uc</name><affiliation wicri:level="2"><nlm:affiliation>Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. ergun-uc@uiowa.edu</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas</wicri:regionArea><placeName><region type="state">Arkansas</region></placeName></affiliation></author><author><name sortKey="Dienel, Gerald A" sort="Dienel, Gerald A" uniqKey="Dienel G" first="Gerald A" last="Dienel">Gerald A. Dienel</name></author><author><name sortKey="Cruz, Nancy F" sort="Cruz, Nancy F" uniqKey="Cruz N" first="Nancy F" last="Cruz">Nancy F. Cruz</name></author><author><name sortKey="Harik, Sami I" sort="Harik, Sami I" uniqKey="Harik S" first="Sami I" last="Harik">Sami I. 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Uc</name><affiliation wicri:level="2"><nlm:affiliation>Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. ergun-uc@uiowa.edu</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas</wicri:regionArea><placeName><region type="state">Arkansas</region></placeName></affiliation></author><author><name sortKey="Dienel, Gerald A" sort="Dienel, Gerald A" uniqKey="Dienel G" first="Gerald A" last="Dienel">Gerald A. Dienel</name></author><author><name sortKey="Cruz, Nancy F" sort="Cruz, Nancy F" uniqKey="Cruz N" first="Nancy F" last="Cruz">Nancy F. Cruz</name></author><author><name sortKey="Harik, Sami I" sort="Harik, Sami I" uniqKey="Harik S" first="Sami I" last="Harik">Sami I. Harik</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><imprint><date when="2002" type="published">2002</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adrenergic beta-Agonists (pharmacology)</term><term>Adrenergic beta-Antagonists (pharmacology)</term><term>Animals</term><term>Antiparkinson Agents (metabolism)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Blood-Brain Barrier (drug effects)</term><term>Brain (blood supply)</term><term>Brain (drug effects)</term><term>Cerebrovascular Circulation (physiology)</term><term>Levodopa (metabolism)</term><term>Levodopa (therapeutic use)</term><term>Male</term><term>Parkinson Disease (drug therapy)</term><term>Rats</term><term>Rats, Wistar</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Adrenergic beta-Agonists</term><term>Adrenergic beta-Antagonists</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="blood supply" xml:lang="en"><term>Brain</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Blood-Brain Barrier</term><term>Brain</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Cerebrovascular Circulation</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Male</term><term>Rats</term><term>Rats, Wistar</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We sought to determine whether beta-adrenergic agonists enhance the brain extraction of L-dopa and L-leucine. Systemic administration of beta-adrenergic agonists increase brain concentrations of L-dopa and other large neutral amino acids (LNAA) in rats and monkeys and may improve symptoms and reduce daily L-dopa requirement in patients with Parkinson's disease. Cerebral blood flow (CBF) using [3H]nicotine and the extraction fraction of 14C-labeled L-dopa or L-leucine were measured simultaneously in various brain regions of conscious rats using the dual-isotope indicator fractionation technique after intraperitoneal administration of isoproterenol (a peripheral nonselective beta-adrenergic agonist), or clenbuterol (a beta2-adrenergic agonist that crosses the blood-brain barrier), or beta-adrenergic agonist preceded by nadolol (a peripheral nonselective beta-adrenergic antagonist), or saline vehicle. Both beta-adrenergic agonists increased regional brain extraction fraction of L-dopa and L-leucine tracers by 35-45%, without altering regional CBF. These changes were accompanied by about a 30% decrease in plasma branched chain LNAA concentrations. Nadolol blocked all these effects. beta-Adrenergic agonists increase the brain extraction of L-dopa and leucine, mainly by peripheral mechanisms that reduce the levels of other competing plasma LNAAs for transport. Thus, beta-adrenergic agonists might be useful in the treatment of patients with Parkinson's disease by enhancing delivery of L-dopa to the brain.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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