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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<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>
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<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>
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<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>
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<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>
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