Involvement of heparan sulfate in 67Ga binding to rat-liver plasma membrane

The role of heparan sulfate (HS) in gallium citrate Ga 67 binding to rat-liver plasma membrane was investigated. HS was found to be the only acid mucopolysaccharide present on the plasma-membrane surface. The extent of 67Ga binding to the plasma membrane reached a plateau 1-2 h after the start of incubation, and binding was higher under alkaline conditions than under acidic conditions. The amount of binding increased in parallel with the protein concentration of the plasma membrane (up to 2 mg per incubation mixture). Solubilizing agents, such as bromelin and 1% Triton X-100 as well as 2 M NaCl and heparin, markedly decreased 67Ga binding, and the decrease in 67Ga binding to the plasma membrane was closely associated with the amount of HS released from the plasma-membrane surface by each solubilizing agent. On the other hand, treatment with HS markedly increased 67Ga binding to about three times the control level. These data provide further support for our previous proposal that HS plays an important role as a receptor for gallium in various tissues, including tumor cells and inflammatory tissues.