Urea alters set point volume for K-Cl cotransport, Na-H exchange, and Ca-Na exchange in dog red blood cells

Urea equilibrates rapidly across the red blood cells of mammals. It was speculated that urea might affect the cell volume sensor by virtue of its properties as a protein perturbant. At concentrations of 0.1-0.6 M, urea caused a decrease in the set points for shrinkage-induced Na-H exchange, swelling-induced K-Cl cotransport, and swelling-induced Ca-Na exchange of dog red blood cells. Okadaic acid opposed the action of urea on all three pathways. The effects were reversible and not due to cyanate. Formamide and acetamide had actions similar to urea but not as potent. Equimolar concentrations of methanol had no effect. The coordinated influence of urea on three separate volume-activated transporters suggests that it acts on a mutual regulatory system that senses and transduces volume stimuli.