1: Eur J Biochem 1995 Apr 15;229(2):419-25
Adenosine inhibits protein synthesis in isolated rat hepatocytes. Evidence
for a lack of involvement of intracellular calcium in the mechanism of
inhibition.
Tinton SA, Chow SC, Buc-Calderon PM, Kass GE, Orrenius S
Departement des Sciences Pharmaceutiques, Universite Catholique de Louvain,
Bruxelles, Belgium.
Extracellularly added adenosine and ATP are potent inhibitors of protein
synthesis in liver cells. In this study, the possible involvement of Ca2+
in the mechanism of inhibition of protein synthesis by adenosine was investigated.
Stimulation of freshly isolated hepatocytes with adenosine or ATP, at concentrations
that impaired protein synthesis, induced an increase in the cytosolic free
Ca2+ concentration ([Ca2+]i). However, there was no correlation between
the increase in [Ca2+]i and inhibition of radiolabelled leucine incorporation
into proteins. Thus, the stimulation of hepatocytes with the V1-receptor
agonist, vasopressin, or with the nucleotide triphosphates, UTP and GTP,
elicited changes in [Ca2+]i similar to those observed after ATP or adenosine
addition, but did not affect protein synthesis. ATP produced near complete
discharge of Ca2+ from the inositol 1,4,5-trisphosphate-sensitive Ca2+
pool in isolated hepatocytes, whereas adenosine only had a partial effect.
Depletion of the hormone-sensitive Ca2+ pool by adenosine was transient.
In contrast, prolonged depletion of internal Ca2+ by thapsigargin resulted
in the inhibition of protein synthesis in hepatocytes. However, the inhibition
of radiolabelled leucine incorporation into proteins by thapsigargin was
further augmented by the additional presence of adenosine. These results
show that the inhibition of protein synthesis by adenosine in isolated
hepatocytes is not mediated by an increase in [Ca2+]i or depletion of internal
pool(s) sensitive to inositol 1,4,5-trisphosphate or thapsigargin.
PMID: 7744064, UI: 95262705