Regulation of amino acid uptake into cerebral microvessels.
The carrier-mediated transport systems, found in cerebral endothelium, are responsible for maintaining the nutrient milieu of the CNS. The objective of this study was to identify what factors might regulate the sodium-dependent A-system of neutral amino acid transport in isolated cerebral microvessels. The uptake of amino acids into isolated microvessels was measured using methylaminoisobutyric acid (MeAIB) a nonhydrolyzable A-analog of the A-system carrier. The results indicated that stimulation of adrenergic (both alpha and beta) receptors significantly (P less than 0.05-0.02) increased the uptake of MeAIB. While the muscarinic agonist carbachol alone did not alter the uptake of MeAIB, it blocked the stimulation evoked by adrenergic agonists. Furthermore, addition of the metal ion, aluminum also significantly (P less than 0.05) increased specific uptake of MeAIB by 95%, when compared to untreated controls. These results indicate that the uptake of neutral amino acids, through the A-system, into cerebral microvessels, can be modulated by adrenergic and cholinergic receptors, as well as the metal ion aluminum. Since the A-system of amino acid transport may control appropriate levels of amino acids in brain, modulation of the uptake of amino acids by adrenergic and cholinergic receptors and by aluminum, may be associated with an imbalance of amino acids and possible neurotransmitter defects in the CNS.
Grammas
P
P
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Kwaiser
T M
TM
Caspers
M L
ML
D000535:Aluminum / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier; D002196:Capillaries / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002560:Cerebrovascular Circulation; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008833:Microcirculation / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000378:metabolism
D000596:Amino Acids; D015091:beta-Alanine; C012924:2,2-dimethyl-beta-alanine; D010656:Phenylephrine; D002217:Carbachol; D011433:Propranolol; D000535:Aluminum; D007545:Isoproterenol