XXXX mobilisation and @entity20648 secretion induced by modified @entity1718 and latex microspheres reveal dual receptor mechanisms for lipid stimulation of @entity70924 cells.

@entity844 @entity70924 @entity19 @entity27146 @entity8586 @entity460 @entity2865 @entity1718 @entity20648 @entity597
How @entity1718 stimulate enteroendocrine cells to release @entity8586 ( @entity20648 ) is largely unknown. Recently, we proposed that the @entity19 enteroendocrine cell line, @entity70924 , responds to insoluble @entity844 aggregates rather than @entity844 monomers in solution. This hypothesis led to two testable predictions. First, other insoluble particles of similar size but unrelated to @entity844 may be able to stimulate @entity70924 cells in a similar fashion to @entity27146 and second, @entity844 sensing in @entity70924 cells should be fairly insensitive to chemical modifications of the @entity844 as long as these modifications do not greatly alter the ability of the molecule to form insoluble aggregates. We used several analogues of @entity27146 and several varieties of latex microsphere (varying in size and surface charge) to see whether the predictions of our model hold. We found that while there was at least one latex microsphere that could induce @entity20648 secretion and @entity460 mobilisation in @entity70924 cells, there was a very poor correlation between the presence of insoluble aggregates and a cellular response. Instead the most important property, determining the potency of @entity844 analogues as stimulants of @entity20648 secretion, was their amphipathicity. Removal of either the polar head or lipophilic tail completely abolished the ability of a given @entity844 analogue to stimulate @entity70924 cells. These data suggested that while @entity1718 can stimulate cells as aggregates, they may also be acting in monomeric form with the oil:water partitioning coefficient playing a crucial role. We finally resolved this issue with the observation that the @entity597 ion greatly altered the response of @entity70924 cells to monomeric @entity27146 . In the presence of @entity597 , @entity70924 cells will only respond to @entity27146 aggregates whereas when @entity597 is replaced with @entity2865 the cells clearly respond to @entity27146 monomers which are completely in solution. In summary, we propose that @entity27146 can stimulate @entity70924 cells via two separate pathways one involving @entity844 monomers in solution and one involving @entity844 aggregates. Which pathway dominates depends on the presence of @entity597 in the extracellular medium.
