Use of tributyltin to probe contribution of Cl(-)-HCO3- exchange to regulation of steady-state pHi in human neutrophils.
Organotin derivatives represent a class of artificial ionophores that mediate Cl(-)-OH- exchange and thereby facilitate the chemical equilibrium distribution of Cl- and H+ across biological membranes. Imposing different pH and Cl- gradients by varying extracellular pH (pHo) and extracellular [Cl-] in the presence of 1 microM tributyltin validated the above assumptions in human neutrophils. Under relatively alkaline conditions [intracellular pH (pHi) greater than or equal to 7.10 and pHo greater than or equal to 7.40], the cell's natural Cl(-)HCO3- exchanger mimicked the actions of the tributyltin compound and was the principal factor controlling steady-state pHi. However, with increasing extracellular acidification, there was a progressive deviation from the predicted equilibrium distribution in the case of the normal Cl(-)-HCO3- transport system, whereas tributyltin-treated cells followed theoretical expectations. Exposure of neutrophils to a number of inhibitors of Cl(-)-HCO3- exchange led to a fall in pHi, apparently confirming the impression that a net HCO3- influx through Cl(-)-HCO3- countertransport was chiefly responsible for maintaining steady-state pHi. However, this intracellular acidification could be satisfactorily ascribed to proton movements through a parallel pathway, namely nonionic diffusion of the free acid form of the drugs. These results imply that Cl(-)-HCO3- exchange is the dominant pH regulatory device only under relatively alkaline conditions and that other mechanisms in addition to Na(+)-H+ exchange are likely to play an important role in recovery from acidification and in maintaining steady-state pHi. The possibility that the lactate carrier may function in this capacity is discussed.
Simchowitz
L
L
Department of Medicine, Veterans Affairs Medical Center, St. Louis, Missouri.
Textor
J A
JA
Vogt
S K
SK
D002352:Carrier Proteins / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007463:Iodobenzoates; D007700:Kinetics; D008433:Mathematics; D009504:Neutrophils / Q000378:metabolism*; D009994:Osmolar Concentration; D012459:Salicylates / Q000494:pharmacology; D014220:Trialkyltin Compounds
D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D007463:Iodobenzoates; D012459:Salicylates; D014220:Trialkyltin Compounds; C020891:3,5-diiodosalicylic acid; C011559:tributyltin