Peptide hormone-membrane interactions. Intervesicular transfer of lipophilic gastrin derivatives to artificial membranes and their bioactivities.

Incorporation of di-fatty acylglycerol moieties at the N-terminus of human little-gastrin-(2-17) leads to self-aggregation of the resulting lipo-gastrins into stable, most probably fluid vesicles. Net intervesicular transfer of the lipo-gastrins to phosphatidyl-choline model bilayers occurs at high rates whereby the chain length of the gastrin lipid moiety was found to affect the transfer rate more decisively than the nature of the acceptor vesicle. Similarly, the bioactivity of the lipo-gastrins is again affected by the nature of the lipid moiety suggesting differentiated interdigitation with the natural bilayer components and thus, different two-dimensional migration rates to the target receptors. Embedment of the lipo-gastrins in phosphatidylcholine bilayers at high lipid/gastrin ratios as mimicry of the cell membrane bound state does not result in onset of ordered structure, but leads to full exposure of the gastrin in essentially randomly coiled form at the water/lipid interface. This may result from the artificial N-terminal anchorage of the gastrin molecules to the bilayers, but also from the relatively tight packing of the phosphatidylcholine vesicles. Nevertheless, this observation might suggest that in the present case membrane-induced conformation and orientation may not represent a pre-requisite for the hormone receptor binding process. However, the results of this study clearly confirm even for the non-amphiphilic hormone gastrin a membrane-bound pathway for receptor recognition and occupancy.