β-Adrenergic regulation of amine precursor amino acid transport across the blood-brain barrier

Abstract

β-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 μmol/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 ED 50 of 0.25 μmol/kg. Salbutamol ( β 2-adrenoceptor agonist, 10 μmol/kg) showed similar effects, but dobutamine ( β 1-adrenoceptor agonist, 50 μmol/kg) failed to increase brain amino acid levels. When l-threo-3,4-dihydroxyphenylalanine (L-DOPA, 100 μmol/kg) was i.p. loaded, β-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 β 2-adrenoceptors and that co-administration of β 2-adrenoceptoragonists with L-DOPA may enhance the therapeutic efficacy of L-DOPA.