Metabolic energy and cytoskeletal requirements for synthesis and secretion by acini from rat mammary gland-I. Ultrastructural and biochemical aspects of synthesis and release of milk proteins.

1. Incubation of acini (alveoli) from lactating rat mammary gland with metabolic and cytoskeletal inhibitors produced a variety of effects on cell function. Cell viability was maintained during incubation as determined by the measurement of lactate dehydrogenase (LDH) activity in media and by light and electron microscopic examination. Caseins and whey proteins were found to be secreted by acini. 2. Addition of iodoacetate, 2,4-dinitrophenol, cyanide, cycloheximide, vinblastine or cytochalasin B inhibited both synthesis and secretion of milk proteins. Colchicine had no effect on synthesis but specifically inhibited protein secretion. Characteristic ultrastructural changes were produced by each inhibitor. 3. Uptake of 2-amino-isobutyric acid was reduced after incubation with all inhibitors except iodoacetate and dinitrophenol. Uridine incorporation was inhibited by colchicine, vinblastine, cytochalasin B and, at high concentrations, 2,4-dinitrophenol; cyanide and cycloheximide stimulated uridine incorporation. 4. Based on these results, milk protein secretion appeared to depend on continued protein synthesis and both processes were energy coupled. Microtubules and microfilaments also appeared to be involved in milk protein secretion.