Epidermal growth factor: intracellular Ca2+ inhibits its association with pancreatic acini and A431 cells

The uptake of 125I-labeled epidermal growth factor (125I-EGF) by mouse pancreatic acini was inhibited (40-50%) by the secretagogue cholecystokinin octapeptide (CCK8). Analysis of competitive binding data showed that the apparent Kd of EGF binding increased 135% while the binding capacity was only slightly altered (30% increase). That the effect of CCK8 on acini was mediated by intracellular Ca2+ was indicated by the following: (i) Inhibition of 125I-EGF binding to acini was dose-dependent and paralleled the known abilities of CCK8, its analogs, and the cholinergic secretagogue carbachol to induce Ca2+ efflux from acini; and (ii) addition of the Ca2+ ionophore A23187 also inhibited 125I-EGF binding. In addition, EGF association with A431 cells was also inhibited by A23187 in the presence but not the absence of Ca2+.