Dimethyl sulfoxide decreases specific EGF binding

Dimethyl sulfoxide (DMSO) stimulates tyrosine phosphorylation of the hepatic EGF receptor in isolated membrane preparations. To determine whether DMSO affects EGF binding, primary cultures of rat hepatocytes were incubated with 1-10% DMSO for 30 min prior to the addition of 125I-EGF. DMSO (1-2%) reduced specific 125I-EGF binding; the effect was maximal (a 40-60% reduction) at 5-7.5% DMSO and was reversed by removing the DMSO. Scatchard analysis showed that the reduction in binding was due to a change in receptor affinity. The decrease in binding was not seen when other, slightly less polar, solvents (eg, acetone and ethanol) were tested. DMSO also reduced 125I-EGF binding to purified rat liver plasma membranes. This reduction was seen in the absence of added ATP and in membranes that had been pretreated with TLCK, a tyrosine kinase inhibitor. Thus, completion of the receptor autophosphorylation reaction was not necessary to effect the change. The data are consistent with a DMSO-induced alteration of receptor conformation that reversibly reduces receptor affinity.