Effects of cytochalasin B on the synthesis and secretion of plasma proteins by developing rat liver.

Abstract

Antimicrotubular drugs such as colchicine impair plasma protein secretion markedly less from developing liver than from mature tissue, suggesting the reduced participation of microtubules in hepatic protein secretion during liver development. In order to evaluate the possible contribution of microfilaments to protein export by immature liver, we incubated slices prepared from adult and gestation day 19 fetal rat liver for up to 4 h with the antimicrofilamentous agent cytochalasin B and with colchicine in various concentrations. In adult tissue, cytochalasin B did not reduce either the synthesis or secretion of [14C]leucine-labeled proteins and albumin. Cytochalasin B decreased apparent albumin synthesis by fetal liver, but otherwise, its effects on [14C]leucine incorporation did not differ from those observed in the adult. In contrast with leucine, the uptake of [3H]glucosamine into both adult and fetal liver was reduced by cytochalasin B. When this reduced uptake was normalized to that in corresponding control incubations, [3H]glucosamine incorporation into glycoproteins was markedly diminished in fetal slices, but was unaffected in the adult. Despite this age-dependent difference, cytochalasin B only minimally affected glycoprotein secretion in each group. Cytochalasin B never modified the antisecretory effects of colchicine. These results suggest that during early development, liver protein synthesis is more sensitive to toxic effects of cytochalasin B than during adulthood. However, microfilaments are not required for plasma protein export at either time.