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Extracellular calcium modulates prereplicative cyclic AMP surges in EGF‐stimulated primary neonatal rat Hepatocytes
Author(s) -
Armato U.,
Ribecco Maria,
Guerriero Chiara,
Testolin Lucia,
Whitfield J. F.
Publication year - 1994
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041610108
Subject(s) - dna synthesis , extracellular , mitosis , calcium , dna replication , epidermal growth factor , hepatocyte , biology , medicine , endocrinology , dna , microbiology and biotechnology , chemistry , biochemistry , receptor , in vitro
The cells in nearly pure (96‐98%) primary cultures of hepatocytes from neonatal rat liver in high (1.0 mM)‐Ca 2+ , serum‐free, synthetic HiWo 5 Ba 2000 medium initiated DNA synthesis and entered mitosis between 11 and 30 h after the addition of 10 ng/ml EGF. During the 10‐h prereplicative period, the cultured hepatocytes, like regenerating rat liver cells, generated two large cyclic AMP transients, one peaking between 30 min and 2 h and the other around 6 h. Hepatocytes stimulated by the same concentration of EGF in low (0.02 mM)‐Ca 2+ medium increased cyclic AMP synthesis as much as the EGF‐treated hepatocytes in high‐Ca 2+ medium, but they released the additional cyclic AMP into the medium and could not generate prereplicative internal cyclic AMP surges, initiate DNA replication, or enter mitosis. These results suggest that one of the ways external Ca 2+ controls prereplicative development of hepatocytes is to restrain the release of cyclic AMP and thus enable the cell to accumulate enough internal cyclic AMP to stimulate events required to initiate DNA replication. © 1994 Wiley‐Liss, Inc.