Effects of phenothiazines on binding and processing of epidermal growth factor in 3T3 cells
Selinfreund, R.; Lin, P.H.; Cooper, J.L.; Wharton, W.
American Journal of Physiology 251(6 Pt 1): C904-C911
1986
ISSN/ISBN: 0002-9513 PMID: 3491545 Document Number: 280100
Chlorpromazine (CPZ) or the functionally related N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide caused a rapid decrease in binding of 125I-epidermal growth factor (EGF) that was due to a specific decrease in receptor affinity. The decrease in ligand binding was observed when cells were exposed to CPZ at either 4.degree. C or 37.degree. C but a rapid reversal of CPZs effects was observed only during at 37.degree. C incubation. In contrast to the decrease in 125I-EGF binding seen after short (30 min) accumulations at 37.degree. C, the presence of CPZ caused a large increase in the amount of cell-associated radioactivity after longer periods (over 1 h) of accumulation. Although the CPZ-induced effect was similar in extent to that observed after the addition of methylamine, the increased accumulation after CPZ was probably not due to a nonspecific ionic neutralization of the lysosomes. CPZ did not lower EGF binding in cultures chronically treated with a phorbol ester to reduce protein kinase C levels, although the CPZ-induced increases in accumulation were still observed in cells with reduced protein kinase C activity.