STUDIES ON THE EFFECT OF INSULIN-LIKE GROWTH FACTOR-I ON CATECHOLAMINE SECRETION FROM CHROMAFFIN CELLS

Abstract: Chromaffin cells cultured in serum‐free medium secreted a smaller percentage of their catecholamine stores in response to stimulation by high K+ (55 mM) than did cells cultured in serum‐containing medium. Addition of insulin‐like growth factor‐I (IGF‐I) to serum‐free medium restored high K+‐stimulated catecholamine secretion to the levels seen in serum‐treated cultures. In contrast, addition of IGF‐I to serum‐containing medium had little effect on catecholamine secretion. These results suggest that serum contains IGF‐I or another factor that maintains the secretory responsiveness of chromaffin cells. IGF‐I not only enhanced high K+‐stimulated catecholamine secretion, but also augmented secretion elicited by the nicotinic agonist dimethyl‐phenylpiperazinium, the dihydropyridine agonist Bay K 8644, and Ba2+. IGF‐I did not affect the dependence of catecholamine secretion on extracellular Ca2+ concentration nor did it affect the time course of secretion. Experiments using 45Ca2+ demonstrated that IGF‐I treatment enhanced Ca2+ uptake into the cells. When cells were permeabilized by treatment with digitonin, Ca2+‐dependent catecholamine secretion was slightly, but consistently, greater from IGF‐I‐treated cells than from untreated cells. Our results suggest that IGF‐I may enhance catecholamine secretion partly by increasing Ca2+ entry into the cells and partly by affecting a step distal to Ca2+ entry. Copyright © 1990, Wiley Blackwell. All rights reserved