Geranylgeranylacetone, an anti-ulcer drug, stimulates hexosamine production in a rat gastric mucosal cell line through binding to a specific cytosolic protein.
An anti-ulcer drug, geranylgeranylacetone (GGA), stimulates hexosamine production in a rat gastric mucosal cell line (RGM-1). The aim of this study was to elucidate the mechanism of this action. The role of protein kinase A, inositol phospholipid turnover and tyrosine kinase in the stimulatory action of GGA on hexosamine production in RGM-1 was determined by observing cAMP production, [3H]-inositol phosphate turnover and western blotting of tyrosine phosphorylation, respectively. Any trophic effect of GGA on RGM-1 was also checked by [3H]-thymidine incorporation. Our experiments showed that GGA has no effect on cAMP production, inositol phospholipid turnover, tyrosine phosphorylation or DNA synthesis in RGM-1. Finally, a [14C]-GGA competitive receptor binding assay was performed on RGM-1 and we found that [14C]-GGA specifically bound to RGM-1 cytosolic protein. Although retinoic acid (RA), another polyisoprenoid compound significantly stimulated hexosamine production in RGM-1, we confirmed that the [14C]-GGA binding site in RGM-1 is different from the RA binding site. In summary, GGA stimulates hexosamine production in RGM-1 and this action is probably mediated through its binding to a specific cytosolic protein in RGM-1.
Hassan
S
S
Department of Medicine, Kobe University School of Medicine, Japan.
Kinoshita
Y
Y
Okada
A
A
Maekawa
T
T
Fukui
H
H
Chiba
T
T
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004224:Diterpenes / Q000378:metabolism / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006595:Hexosamines / Q000096:biosynthesis*; D007295:Inositol Phosphates / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D006595:Hexosamines; D007295:Inositol Phosphates; D018160:Receptors, Cytoplasmic and Nuclear; D004247:DNA; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; C031049:geranylgeranylacetone