Chloroquine affects prolactin secretion and Golgi morphology in the mammotroph

Chloroquine is widely used as a lysosomal enzyme inhibitor, and while effects on DNA repair and membrane recycling have also been reported, there has been no investigation of effects on the processing of secretory products. To determine whether chloroquine had any effect on secretion and secretory organelles, we monitored the effects of low concentrations (10(-6) M) of chloroquine on a cell population which normally secretes copious amounts of a simple polypeptide (PRL) in vitro and in which there exists a subpopulation of cells which releases PRL very rapidly after synthesis. Cultured anterior pituitary cells were exposed to 10(-6) M chloroquine for 6, 12, 24, or 48 h. At these times, the culture medium was used for determination of PRL content and beta-glucuronidase activity, and the cells were used for determination of DNA content and level of beta-glucuronidase activity or for electron microscopy. Treatment with 10(-6) M chloroquine resulted in 20-40% inhibition of PRL release (maximum inhibition at any dose), no change in the total amount of beta-glucuronidase activity, and a number of ultrastructural changes in the Golgi region consistent with an accumulation of chloroquine within the cisternae and immature granules. The effects of chloroquine on Golgi morphology were unaltered by cotreatment with 50 micrograms/ml cycloheximide, and chloroquine had no affect on PRL synthesis. These results are consistent with an adverse effect of chloroquine on packaging of PRL into immature granules in the Golgi apparatus, without any effect on the release of mature secretory granules.