title: Transport activities involved in intracellular pH recovery following acid and alkali challenges in rat brain microvascular endothelial cells.
abstract: Transport activities involved in intracellular pH (pH(i)) recovery after acid or alkali challenge were investigated in cultured rat brain microvascular endothelial cells by monitoring pH(i) using a pH-sensitive dye. Following relatively small acid loads with pH(i) approximately 6.5, HCO(-)(3) influx accounted for most of the acid extrusion from the cell with both Cl(-)-independent and Cl(-)-dependent, Na(+)-dependent transporters involved. The Cl(-)-independent component has the same properties as the NBC-like transporter previously shown to account for most of the acid extrusion near the resting pH(i). Following large acid loads with pH(i) < 6.5, most of the acid extrusion was mediated by Na(+)/H(+) exchange, the rate of which was steeply dependent on pH(i). Concanamycin A, an inhibitor of V-type ATPase, had no effect on the rates of acid extrusion. Following an alkali challenge, the major component of the acid loading leading to recovery of pH(i) occurred by Cl(-)/HCO(-)(3) exchange. This exchange had the same properties as the AE-like transporter previously identified as a major acid loader near resting pH(i). These acid-loading and acid-extruding transport mechanisms together with the Na(+), K(+), ATPase may be sufficient to account not only for pH(i) regulation in brain endothelial cells but also for the net secretion of HCO(-)(3) across the blood-brain barrier.
authors.affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK.
authors.forename: Pieris A
authors.initials: PA
authors.lastname: Nicola
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Taylor
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.forename: Margery A
authors.initials: MA
authors.lastname: Barrand
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Hladky
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000378:metabolism; D000143:Acids / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000468:Alkalies / Q000378:metabolism*; D000584:Amiloride / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D001921:Brain / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D002254:Carbonates / Q000378:metabolism; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008833:Microcirculation; D018696:Neuroprotective Agents / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism
chemical_list: D000143:Acids; D000468:Alkalies; D002254:Carbonates; D002712:Chlorides; D018696:Neuroprotective Agents; D000584:Amiloride; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D012964:Sodium; D025262:Vacuolar Proton-Translocating ATPases; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; C039614:ethylisopropylamiloride