The effect of trifluoperazine on the phosphorylation of ribosomal small subunit protein S6 in D-galactosamine-injured and normal rat liver.
The effect of the Ca2+-calmodulin antagonist trifluoperazine on the elevation of phosphorylation of rat liver small ribosomal subunit protein S6 induced by the hepatotoxic agent D-galactosamine has been studied. Trifluoperazine applied in various doses (1-100 mg/kg body wt) before injection of D-galactosamine into the rat does not reverse the strong increase in phosphorylation promoted by D-galactosamine. Instead, trifluoperazine has been identified as a potent stimulator of S6 phosphorylation in normal rat liver in vivo without causing significant changes in the cyclic AMP content of liver and the overall rate of liver protein synthesis. Both drugs, however, were not effective in stimulating the incorporation of [32P]phosphate into microsomes or crude ribosomes in liver slices in vitro. The results suggest that a calmodulin-activated protein kinase probably is not primarily engaged in S6 phosphorylation produced by D-galactosamine. However, further in vitro studies are needed to reach a definite conclusion.
D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000378:metabolism; D005688:Galactosamine / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins / Q000378:metabolism*; D014268:Trifluoperazine / Q000494:pharmacology*; D014633:Valine / Q000378:metabolism
D002147:Calmodulin; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; D014268:Trifluoperazine; D005688:Galactosamine; D000242:Cyclic AMP; D014633:Valine