Abstract
Livers of normal mice were prefused in situ and the secretion of newly synthesized (i.e. labeled) proteins into the perfusate were measured. In control livers, the secretion of newly synthesized proteins was found to be linear with time. In marked contrast, when livers were perfused with vinblastine, vincristine, or colchicine, drugs known to interfere with the hepatic microtubular system, the release of newly synthesized proteins was either strongly inhibited or completely suppressed although total hepatic protein synthesis (estimated by the incorporation of labeled amino acids into hepatic plus perfusate proteins) remained unaltered. Chromatographic separation of the various secreted proteins showed that the release of albumin, globulins, and small polypeptides was decreased to a similar extent by vincristine or colchicine. In the particular case of albumin, it was further observed that total (i.e. liver plus perfusate) labeled amino acid incorporation into albumin was not altered by either vincristine or colchicine, whereas the incorporation of these amino acids into liver albumin was markedly increased but incorporation into perfusate albumin was decreased, suggesting that the translocation of this particular protein from the liver to the perfusate had been affected by the presence of these drugs. It is proposed that the functional integrity of microtubules is necessary for the intracellular movement and eventual release of albumin and other proteins by the liver, and suggested that microtubules might possibly be a site of regulation of hepatic protein secretion.