Beta-adrenergic regulation of amine precursor amino acid transport across the blood-brain barrier.
Beta-Adrenoceptor agonists were administered i.p. into rats and amino acid levels in brain and plasma were then determined to assess the effects on transport across the blood-brain barrier. Isoproterenol (10 mumol/kg) caused significant increases in aromatic amino acid (tyrosine, phenylalanine and tryptophan) levels in cerebral cortex and decreases in almost all amino acid concentrations in plasma. This effect of isoproterenol on brain tyrosine level was dose-dependent with an ED50 of 0.25 mumol/kg. Salbutamol (beta 2-adrenoceptor agonist, 10 mumol/kg) showed similar effects, but dobutamine (beta 1-adrenoceptor agonist, 50 mumol/kg) failed to increase brain amino acid levels. When 1-threo-3,4-dihydroxyphenylalanine (L-DOPA, 100 mumol/kg) was i.p. loaded, beta-adrenoceptor agonists promoted the transport of L-DOPA into brain without increasing the clearance rate of plasma L-DOPA. Moreover, significant increases in dopamine and its metabolites were observed in rat brain. These findings suggest that the transport of aromatic amino acids across the blood-brain barrier may be regulated through beta 2-adrenoceptors and that co-administration of beta 2-adrenoceptor agonists with L-DOPA may enhance the therapeutic efficacy of L-DOPA.
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan.
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Takao
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Kamisaki
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Itoh
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007980:Levodopa / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000596:Amino Acids; D001679:Biogenic Amines; D011943:Receptors, Adrenergic, beta; D014443:Tyrosine; D007980:Levodopa; D007545:Isoproterenol; D004298:Dopamine