Recently, the presence of both influx and efflux molecular water pumps (MWP
's) in vertebrate cells has been reported. These appear to use a common mec
hanism; the intercompartmental cotransport of water uphill against a gradie
nt as a hydrophylic osmolyte is transported down its own gradient, in a reg
ulated fashion, by a membrane spanning cotransporter protein. In each case,
the dwell rime of the transported osmolyte is short in that it is metaboli
cally converted and its products either eliminated or recycled, thereby mai
ntaining the required high intercompartmental gradient. An influx water pum
p osmolyte has been identified as a sodium-glucose complex, and an efflux w
ater pump osmolyte as N-acetylhistidine These osmolytes may also be archety
pal representatives of many other osmolytes with similar Functions in a var
iety of cells. When recycled, the osmolyte metabolites appear to be dewater
ed during high affinity binding that is associated with their active transp
ort back across the membrane prior to intracellular resynthesis of the osmo
lyte. Since these cyclical systems result in the pumping of water, they als
o appear to create a previously unrecognized motive force which results in
the establishment of unidirectional transcellular water flows between apica
l and basolateral cell membranes, As neurons represent highly specialized f
orms of animal cells, and cells which are also extremely sensitive to chang
es in osmotic pressure. the presence of these water pumps in the CNS could
be significant. There would be connotations with regard to how neurons regu
late water balance and transaxonal flow as well as to how; these factors af
fect the integrated function of the nervous system. In this article, eviden
ce of the presence of MWP's in the nervous system, and how they might relat
e to aspects of both normal and abnormal brain function is reviewed. (C) 19
99 Elsevier Science Ltd. All rights reserved.