Effects of urea on volume-sensitive k-cl cotransport in lk sheep red blood
cells - evidence for two different signals of swelling.
Dunham, Philip B.
Department of Biology, Syracuse University, Syracuse, New York 13244
APStracts 2:0019C, 1995.
K-Cl cotransport in sheep red cells is activated by 0.5 M urea as it is in dog
red cells (Parker Am. J. Physiol. 265 (Cell Physiol. 34): C447-C452, 1993).
The activation proceeds with a delay, like activation by swelling. Swelling of
cells in urea activates K uptake further, but with no delay. Inactivation
following removal of urea also proceeds without delay. With cotransport
partially activated by reducing [Mg]c or with staurosporine, urea did
not activate cotransport further. However swelling activated cotransport
further in these two types of cells. In terms of the three-state process for
swelling-activation of K-Cl cotransport (Dunham et al. J. Gen. Physiol. 101:
733-765, 1993), these results indicate that urea activates the first
conversion, A ---> B, and does so by inhibiting the reverse reaction promoted
by a kinase, just as reducing [Mg]c does. Stimulation of cotransport by
urea is nearly completely reversed by shrinkage, whereas activation by
reducing [Mg]c is reversed only 35%. Therefore urea inhibits the
kinase indirectly, like swelling, by reducing macromolecular crowding of
cytoplasmic proteins (Minton et al. Proc. Natl. Acad. Sci. 89: 10504-10506,
1992). Since swelling activates cotransport in two ways, one mimicked by urea
and one not, there must be two signals of swelling, one a reduction of
macromolecular crowding, and the other probably a mechanical signal.
Received 1 September 1994; accepted in final form 7 November 1994
APS Manuscript Number C0515-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1994 The American Physiological Society.
Published in APStracts on 27 February 1995.