The effects of forskolin and calcium ionophore A23187 on secretion and cytoplasmic RNA levels of Chromogranin-A and calcitonin

Abstract

We have studied the regulation of the secretion and cytoplasmic RNA levels of calcitonin (CT) and Chromogranin-A (CgA) to determine if the biosynthesis and secretion of these two substances are controlled in a coordinated fashion. The studies were conducted in two cell lines, a medullary thyroid carcinoma (MTC) cell line and a lung tumor (BEN) cell line. Both cell types secrete CT and CgA. Forskolin treatment resulted in a significant increase in the secretion of CT and CgA in each cell line and in CT-specific cytoplasmic RNA in the MTC cell line. Treatment with calcium ionophore A23187 resulted in significantly increased secretion of both substances in the lung tumor cells but not in the medullary thyroid carcinoma cells. A significant increase in CT-specific or CgA-specific cytoplasmic RNA was not seen in either cell line. We conclude that the secretion of CT and CgA are regulated in a coordinated fashion in these cell lines through processes that are calcium-mediated and processes that involve cyclic AMP-dependent protein kinase A. However, each of these regulatory pathways is not always operative in a given tissue. The coordinate regulation of the secretion of CT and CgA supports the hypothesis that CgA participates in the secretory process of its associated hormones.