Abstract
The fully active gastrin and CCK analogues [Nle^15^]‐gastrin‐ 17 and [Nle, Thr]‐CCK‐9 were analysed for their Ca^2+^ and Tb^3+^ affinities in various membrane mimetic conditions. In TFE both gastrin and CCK exhibited high affinities for calcium and terbium. At saturation level identical metal ion/peptide ratios were determined with Ca^2+^ and Tb^3+^, i.e. R = 3 for gastrin and R = 1 for CCK, confirming the very similar coordination properties of the two metal ions. The conformational effects of both metal ions were found to be very similar with a disordering effect in the case of gastrin and a conformational transition to β‐turn type structure in the case of CCK. In order to mimic more properly physiological conditions, similar experiments were performed in the prsence of phospholipid bilayers. No interaction of the peptides with the bilayers was observed even in the presence of phospholipid bilayers. No interaction of the peptides with the bilayers was observed even in the presence of mmolar Ca^2+^ concentrations. Induced lipid interaction via N‐terminal lipodervatization of gastrin and CCK allowed to translocate quantitatively the two hormones into phospholipid bilayers and to examine the effect of extravesicular Ca^2+^ on the conformation of the peptide headgroups and on their display at the water/lipid interphase. The CCK moiety of the lipo‐CCK inserted into phospholipid bilayers interacts with the lipid phase and addition of Ca^2+^ enhances the clustering of the peptide headgroups in a more β‐sheet type conformation. Conversely, insertion of lipo‐gastrin into the bilayers leads to full exposure of the gastrin headgroup to the bulk water in predominantly random coil structure. Again Ca^2+^ provokes aggregation. As the lipo‐peptide/phospholipid system still represents only an artificial model, it remains hazardous to derive a biological relevance from these data. The significantly higher affinity of lanthanide ions than Ca^2+^ for the peptides could well play a role in the inhibibitory activity of lanthanum on the signal transduction of the CCK family of hormones.