AJP - Regulatory, Integrative and Comparative Physiology, Vol 262, Issue 5 909-R914, Copyright © 1992 by American Physiological Society
Maturational differences in acetazolamide-altered pH and HCO3 of choroid plexus, cerebrospinal fluid, and brain
C. E. Johanson, Z. Parandoosh and M. L. Dyas
Department of Clinical Neurosciences, Brown University, Providence, Rhode Island.
The carbonic anhydrase inhibitor acetazolamide is useful for analyzing ion
transport, pH regulation, and fluid formation in developing central nervous
system. We used the 14C-labeled dimethadione technique to measure
alterations in steady-state pH, and to estimate the HCO3 concentration
[HCO3], in choroid plexus (CP), cerebrospinal fluid (CSF), and cerebral
cortex of 1- and 3-wk-old Sprague-Dawley rats treated with acetazolamide or
probenecid. These drugs can suppress transport of HCO3 and other anions in
some cells, consequently altering intracellular pH. In 1-wk-old infant rats
whose CSF secretory process is incompletely developed, 1 h of acetazolamide
treatment did not significantly change CP intracellular pH or [HCO3].
However, in 3-wk-old rats, in which the ability of CP to secrete ions and
fluids is almost fully developed, acetazolamide caused marked increases in
CP cell intracellular pH and [HCO3]. In contrast, acetazolamide-induced
alkalinization was not observed in CSF or cerebral cortex of the 1- and
3-wk-old animals. The other test agent, probenecid (an inhibitor of anion
transport but not of carbonic anhydrase), did not alter the pH of any
region at any age investigated. Overall, the results are interpreted in
light of developmental changes in carbonic anhydrase and previous findings
from kinetic analyses of ion-translocating systems in CP. Acetazolamide may
interfere with a CP apical membrane HCO3 extrusion mechanism not fully
operational in infant rats.
