Blood-brain barrier taurine transport during osmotic stress and in focal cerebral ischemia.
Little is known about blood to brain taurine transport despite substantial evidence suggesting a role of taurine in brain volume regulation during osmotic stress or conditions inducing cell swelling, such as ischemia. We have made measurements of the taurine influx rate constant (K1) with [3H]taurine in three conditions: raised plasma taurine concentrations induced by infusion with 50 mM taurine (10 microliters/100 g/min); osmotic stress induced by i.p. injections of 1.5 M NaCl (2 ml/100 g) or distilled water (10 ml/100 g); and 4 h of middle cerebral artery occlusion (MCAo). In rats with MCAo, additional determinations were made of tissue water and taurine contents, and blood-brain barrier passive permeability with [3H]alpha-aminoisobutyric acid. Taurine infusion increased plasma taurine from 110 +/- 63 microM (SD) to 407 +/- 63 (p < 0.001) and decreased taurine K1 at the blood-brain barrier by 70% (p < 0.001), signifying saturable uptake that maintained unidirectional influx constant. Similarly, although hypo- and hyperosmolality increased and decreased plasma taurine concentration, respectively, a reciprocal relationship between K1 and plasma taurine in these experiments ensured that unidirectional fluxes of taurine into brain were unchanged by osmotic stress. During MCAo, the taurine K1 was reduced 80% in the ipsilateral ischemic tissue compared with the contralateral nonischemic tissue (p < 0.001). This decline may be due to a release of taurine into the brain circulation, because there was a concomitant loss of tissue taurine of 7.4 +/- 2.4 mmol/g dry weight (p < 0.05). Alternately, if taurine uptake is sodium dependent, the decline might reflect a disruption of the endothelial sodium gradient.
Stummer
W
W
Department of Surgery, University of Michigan, Ann Arbor 48109-05321, USA.
Betz
A L
AL
Shakui
P
P
Keep
R F
RF
D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier; D002545:Brain Ischemia / Q000378:metabolism*; D006706:Homeostasis; D008297:Male; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000097:blood / Q000493:pharmacokinetics*
D000621:Aminoisobutyric Acids; C100049:2-aminoisobutyric acid; D013654:Taurine