Prostaglandins induce proliferation of rat hepatocytes through a
prostaglandin e2 receptor ep3 subtype.
Hashimoto, Naoaki, Tsuyoshi Watanabe, Yusei Ikeda, Haruki Yamada,
Shigeo Taniguchi, Hiroshi Mitsui, and Kiyoshi Kurokawa.
First Department of Internal Medicine, Faculty of Medicine,
University of Tokyo, Tokyo 113., Department of Gastroenterology,
Tokyo Kosei-Nenkin Hospital, Tokyo 162, Japan
APStracts 3:0254G, 1996.
We characterized the proliferative action of prostaglandins (PGs) in
relation to their membrane receptors on rat hepatocytes in primary
culture. PGs in the order 16, 16-dimethyl PGE2 > PGE2 >
PGF2[alpha], >> PGD2 augmented EGF/insulin-induced DNA
synthesis, assessed by [3H]thymidine incorporation, in a
concentration-dependent manner, whereas PGs alone did not stimulate
basal DNA synthesis without EGF and insulin. The cells exhibited
[3H]PGE2 binding sites which were displaced by unlabeled PGs in the
order PGE1 = PGE2 > PGF2[alpha] > PGD2. PGE2 inhibited
glucagon-stimulated cAMP accumulation concentration-dependently. The
ED50 value for DNA synthesis, IC50 value for cAMP accumulation and Kd
value for [3H]PGE2 binding at 25oC were almost identical (around 70
nM). Treatment of the cells with pertussis toxin (100 ng/ml), which
ADP-ribosylated most of the 41-kDa substrate, abolished the
proliferative effects of PGs. We detected the expression of mRNA of
the EP3 subtype PGE2 receptor employing the reverse transcription
-polymerase chain reaction. Moreover, an EP3 agonist, enprostil, but
not the EP1 agonist, 17-phenyl-trinor-PGE2, or the EP2/EP4 agonist,
11-deoxy-PGE1, stimulated EGF/insulin-induced DNA synthesis. These
results indicate that PGs act as comitogenic growth factors through
the EP3 subtype PGE2 receptor coupled with Gi protein in cultured rat
hepatocytes.
Received 7 August 1996; accepted in final form 30 September 1996.
APS Manuscript Number G334-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996