GERANYLGERANYLACETONE, AN ANTIULCER DRUG, STIMULATES HEXOSAMINE PRODUCTION IN A RAT GASTRIC-MUCOSAL CELL-LINE THROUGH BINDING TO A SPECIFICCYTOSOLIC PROTEIN

An anti-ulcer drug, geranylgeranylacetone (GGA), stimulates hexosamine production in a rat gastric mucosal cell line (RGM-1). The aim of thi s study was to elucidate the mechanism of this action. The role of pro tein kinase A, inositol phospholipid turnover and tyrosine kinase in t he stimulatory action of GGA on hexosamine production in RGM-1 was det ermined by observing cAMP production, [H-3]-inositol phosphate turnove r and western blotting of tyrosine phosphorylation, respectively. Any trophic effect of GGA on RGM-1 was also checked by [H-3]-thymidine inc orporation. Our experiments showed that GGA has no effect on cAMP prod uction, inositol phospholipid turnover, tyrosine phosphorylation or DN A synthesis in RGM-1. Finally, a [C-14]-GGA competitive receptor bindi ng assay was performed on RGM-1 and we found that [C-14]-GGA specifica lly bound to RGM-1 cytosolic protein, Although retinoic acid (RA), ano ther polyisoprenoid compound significantly stimulated hexosamine produ ction in RGM-1, we confirmed that the [C-14]-GGA binding site in RGM-1 is different from the RA binding site. In summary, GGA stimulates hex osamine production in RGM-1 and this action is probably mediated throu gh its binding to a specific cytosolic protein in RGM-1.