AJP - Cell Physiology, Vol 258, Issue 2 C211-C216, Copyright © 1990 by American Physiological Society
Cotransport of sodium and chloride by the adult mammalian choroid plexus
C. E. Johanson, S. M. Sweeney, J. T. Parmelee and M. H. Epstein
Department of Clinical Neurosciences, Brown University/Rhode Island Hospital, Providence 02902.
Cerebrospinal fluid formation stems primarily from the transport of Na and
Cl in choroid plexus (CP). To characterize properties and modulation of
choroidal transporters, we tested diuretics and other agents for ability to
alter ion transport in vitro. Adult Sprague-Dawley rats were the source of
CPs preincubated with drug for 20 min and then transferred to cerebrospinal
fluid (CSF) medium containing 22Na or 36Cl with [3H]mannitol (extracellular
correction). Complete base-line curves were established for cellular uptake
of Na and Cl at 37 degrees C. The half-maximal uptake occurred at 12 s, so
it was used to assess drug effects on rate of transport (nmol Na or Cl/mg
CP). Bumetanide (10(-5) and 10(-4) M) decreased uptake of Na and Cl with
maximal inhibition (up to 45%) at 10(-5) M. Another cotransport inhibitor,
furosemide (10(-4) M), reduced transport of Na by 25% and Cl by 33%.
However, acetazolamide (10(-4) M) and atriopeptin III (10(-7) M)
significantly lowered uptake of Na (but not Cl), suggesting effect(s) other
than on cotransport. The disulfonic stilbene
4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; 10(-4) M), known to
inhibit Cl-HCO3 exchange, substantially reduced the transport of 36Cl.
Bumetanide plus DIDS (both 10(-4) M) caused additive inhibition of 90% of
Cl uptake, which provides strong evidence for the existence of both
cotransport and antiport Cl carriers. Overall, this in vitro analysis,
uncomplicated by variables of blood flow and neural tone, indicates the
presence in rat CP of the cotransport of Na and Cl in addition to the
established Na-H and Cl-HCO3 exchangers.
