Mechanisms of sodium transport at the blood-brain barrier studied with in situ perfusion of rat brain.
The mechanism of unidirectional transport of sodium from blood to brain in pentobarbital-anesthetized rats was examined using in situ perfusion. Sodium transport followed Michaelis-Menten saturation kinetics with a Vmax of 50.1 nmol/g/min and a Km of 17.7 mM in the left frontal cortex. The kinetic analysis indicated that, at a physiologic sodium concentration, approximately 26% of sodium transport at the blood-brain barrier (BBB) was carrier mediated. Dimethylamiloride (25 microM), an inhibitor of Na+/H+ exchange, reduced sodium transport by 28%, whereas phenamil (25 microM), a sodium channel inhibitor, reduced the transfer constant for sodium by 22%. Bumetanide (250 microM) and hydrochlorothiazide (1.5 mM), inhibitors of Na(+)-K(+)-2Cl-/NaCl symport, were ineffective in reducing blood to brain sodium transport. Acetazolamide (0.25 mM), an inhibitor of carbonic anhydrase, did not change sodium transport at the BBB. Finally, a perfusate pH of 7.0 or 7.8 or a perfusate PCO2 of 86 mm Hg failed to change sodium transport. These results indicate that 50% of transcellular transport of sodium from blood to brain occurs through Na+/H+ exchange and a sodium channel in the luminal membrane of the BBB. We propose that the sodium transport systems at the luminal membrane of the BBB, in conjunction with Cl-/HCO3- exchange, lead to net NaCl secretion and obligate water transport into the brain.
Ennis
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Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor 48109-0532, USA.
Ren
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Betz
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D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002560:Cerebrovascular Circulation; D005625:Frontal Lobe / Q000378:metabolism; D006852:Hydrochlorothiazide / Q000494:pharmacology; D007700:Kinetics; D010477:Perfusion; D010953:Plasma Volume; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D028021:Sodium-Potassium-Chloride Symporters
D002352:Carrier Proteins; D015222:Sodium Channels; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D006852:Hydrochlorothiazide; D002034:Bumetanide; C047088:phenylamil; C039465:5-dimethylamiloride; D000584:Amiloride; D012964:Sodium