β-Adrenergics enhance brain extraction of levodopa
Identifieur interne : 006595 ( Main/Merge ); précédent : 006594; suivant : 006596β-Adrenergics enhance brain extraction of levodopa
Auteurs : Ergun Y. Uc [États-Unis] ; Gerald A. Dienel [États-Unis] ; Nancy F. Cruz [États-Unis] ; Sami I. Harik [États-Unis]Source :
- Movement disorders [ 0885-3185 ] ; 2002.
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- Pascal (Inist)
English descriptors
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Abstract
We sought to determine whether (3-adrenergic agonists enhance the brain extraction of L-dopa and L-leucine, Systemic administration of β-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 (3-adrenergic agonist), or clenbuterol (a β2-adrenergic agonist that crosses the blood-brain barrier), or β-adrenergic agonist preceded by nadolol (a peripheral nonselective β-adrenergic antagonist), or saline vehicle. Both β-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. (3-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, β-adrenergic agonists might be useful in the treatment of patients with Parkinson's disease by enhancing delivery of L-dopa to the brain.
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Uc</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, University of Arkansas for Medical Sciences</s1><s2>Little Rock, Arkansas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Arkansas</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Central Arkansas Veterans Healthcare System</s1><s2>Little Rock, Arkansas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><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><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, University of Arkansas for Medical Sciences</s1><s2>Little Rock, Arkansas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Arkansas</region></placeName></affiliation></author><author><name sortKey="Cruz, Nancy F" sort="Cruz, Nancy F" uniqKey="Cruz N" first="Nancy F." last="Cruz">Nancy F. Cruz</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, University of Arkansas for Medical Sciences</s1><s2>Little Rock, Arkansas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Arkansas</region></placeName></affiliation></author><author><name sortKey="Harik, Sami I" sort="Harik, Sami I" uniqKey="Harik S" first="Sami I." last="Harik">Sami I. Harik</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, University of Arkansas for Medical Sciences</s1><s2>Little Rock, Arkansas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Arkansas</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Central Arkansas Veterans Healthcare System</s1><s2>Little Rock, Arkansas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Arkansas</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2002">2002</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Agonist</term><term>Animal</term><term>Antagonist</term><term>Antiparkinson agent</term><term>Biological effect</term><term>Brain (vertebrata)</term><term>Chemotherapy</term><term>Clenbuterol</term><term>Isoprenaline</term><term>Leucine</term><term>Levodopa</term><term>Mechanism of action</term><term>Nadolol</term><term>Rat</term><term>β-Adrenergic receptor agonist</term><term>β2-Adrenergic receptor</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Clenbutérol</term><term>Agoniste</term><term>Récepteur β2-adrénergique</term><term>Stimulant β-adrénergique</term><term>Chimiothérapie</term><term>Antiparkinsonien</term><term>Isoprénaline</term><term>Nadolol</term><term>Antagoniste</term><term>Lévodopa</term><term>Leucine</term><term>Encéphale</term><term>Effet biologique</term><term>Mécanisme action</term><term>Rat</term><term>Animal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We sought to determine whether (3-adrenergic agonists enhance the brain extraction of L-dopa and L-leucine, Systemic administration of β-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 [<sup>3</sup>H]nicotine and the extraction fraction of <sup>14</sup>C-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 (3-adrenergic agonist), or clenbuterol (a β<sub>2</sub>-adrenergic agonist that crosses the blood-brain barrier), or β-adrenergic agonist preceded by nadolol (a peripheral nonselective β-adrenergic antagonist), or saline vehicle. Both β-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. (3-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, β-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><affiliations><list><country><li>États-Unis</li></country><region><li>Arkansas</li></region></list><tree><country name="États-Unis"><region name="Arkansas"><name sortKey="Uc, Ergun Y" sort="Uc, Ergun Y" uniqKey="Uc E" first="Ergun Y." last="Uc">Ergun Y. Uc</name></region><name sortKey="Cruz, Nancy F" sort="Cruz, Nancy F" uniqKey="Cruz N" first="Nancy F." last="Cruz">Nancy F. Cruz</name><name sortKey="Dienel, Gerald A" sort="Dienel, Gerald A" uniqKey="Dienel G" first="Gerald A." last="Dienel">Gerald A. Dienel</name><name sortKey="Harik, Sami I" sort="Harik, Sami I" uniqKey="Harik S" first="Sami I." last="Harik">Sami I. Harik</name><name sortKey="Harik, Sami I" sort="Harik, Sami I" uniqKey="Harik S" first="Sami I." last="Harik">Sami I. Harik</name><name sortKey="Uc, Ergun Y" sort="Uc, Ergun Y" uniqKey="Uc E" first="Ergun Y." last="Uc">Ergun Y. Uc</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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