Regulation of neurotensin content in adrenal medullary cells: comparison of PC12 cells to normal rat chromaffin cells in vitro.

Radioimmunoassay studies of cultures of PC12 pheochromocytoma cells have shown progressive increments in content and release of neurotensin in response to combinations of dexamethasone, nerve growth factor, activators of adenylate cyclase and lithium. We have studied the distribution of immunoreactive neurotensin by immunocytochemistry in cultures of PC12 cells and normal rat chromaffin cells, with two objectives: (i) to determine how changes measured by radioimmunoassay in extracts of PC12 cell populations are manifested at the level of individual cells and (ii) to determine whether normal chromaffin cells respond to combinations of agents similarly to PC12 cells. Staining for immunoreactive neurotensin is not identifiable in PC12 cells maintained in control medium or with any of the medium supplements alone. Approximately 3% of cells are stained after maintenance with dexamethasone plus nerve growth factor, verus 17% with dexamethasone plus nerve growth factor plus forskolin, and 33% with all four agents. This heterogeneity does not appear to result from clonal diversity, or to be cell cycle-dependent. Individual PC12 cells recruited to produce neurotensin in response to particular signals may, however, have passed a critical stage of differentiation toward a chromaffin cell, rather than neuronal phenotype before exposure to those signals. Staining for immunoreactive neurotensin is observed in up to 18% of normal chromaffin cells maintained with dexamethasone plus nerve growth factor, up to 45% with dexamethasone plus nerve growth factor plus forskolin, and up to 54% with all four agents. Proportions of cells stained under the various culture conditions are established before birth and in fetal cultures staining is confined for the most part to cells which do not undergo neuronal differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)