Cellular uptake of cyclic AMP captured within phospholipid vehicles and effect on cell-growth behaviour

Cyclic 3′,5′-adenosine monophosphate (cyclic AMP) was successfully incorporated within unilamellar phospholipid vesicles. Treatment of 3T3 and SV40-transformed 3T3 cells (SV3T3 cells) with vesicles containing cyclic AMP resulted in significant intracellular incorporation of vesicle-associated cyclic AMP and alteration of cell-growth behavior. Vesicles containing cyclic AMP caused a significant reduction in the growth rate of 3T3 and SV3T3 cells and effectively inhibited growth stimulation in stationary 3T3 cell cultures treated with insulin, serum and proteolytic enzymes. These alterations in cell-growth behaviour were produced by vesicle cyclic AMP at concentrations as low as 10^-7 M. Similar modification of cell growth by addition of cyclic AMP or dibutyryl-cyclic AMP to the culture medium was achieved only at concentrations as high as 10^-4 M plus 10^-3 M theophylline. The ability of cyclic AMP trapped within vesicles to modify cell behaviour was influenced by the lipid composition of the vesicles. Cyclic AMP-containing vesicles composed of lipids that were in a "fluid" state of 37 °C produced marked growth inhibition while similar concentrations of cyclic AMP within vesicles prepared from "solid" lipids had no effect on cell proliferation. The influence of vesicle lipid composition on the mechanisms by which vesicles may be incorporated in to cells was discussed.