CELLULAR-DISTRIBUTION OF G-PROTEIN GO-ALPHA IN PITUITARY LACTOTROPHS - EFFECTS OF DOPAMINE

Membrane-bound GTP-binding (G) proteins mediate signal transduction in a variety of cell systems. The exact mechanisms of G proteins action are still under investigation but they appear to involve effecters loc ated in the plasma membrane as well as in other parts of the cell. Wit h this study, we investigated the cellular and ultrastructural localiz ation of G protein subunits, and particularly of Go alpha, in normal r at anterior pituitaries and in estrone-induced rat adenomatous lactotr ophs. We also evaluated the effects of Go alpha cellular redistributio n in rat adenomatous lactotrophs following short-term exposure to dopa mine (DA). Using the Protein A-gold (PAG) methodology, Go alpha was fo und to be present in the cysternae of the endoplasmic reticulum of nor mal pituitary cells and of adenomatous lactotrophs. In the latter, Go alpha could be co-localized with prolactin (PRL). By immunoblots, usin g specific antisera, significant amounts of Go alpha and Gs42 alpha, t ogether with smaller amounts of Gi alpha, Gs47 alpha and G beta were f ound to be present in the uncontaminated supernatant fraction of adeno matous lactotrophs. Unexpectedly, exposure of the cells to DA induced a rapid and short-lived decrease in the cytosolic fraction of Go alpha and G beta associated with a decrease of PRL release. Since cytosolic Go alpha can be ADP-ribosylated by pertussis toxin (PT) and is theref ore in a heterotrimeric form, our data suggest that the soluble Go pro tein may play a role during lactotrophs' exposure to an inhibitor of P RL release, perhaps through its relocalization after being internalize d with the D-2 receptor or by being used for interaction with intracel lular and/or membrane-bound effecters.