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Molecular Pharmacology, Vol 1, 66-76, Copyright © 1965 by the American Society for Pharmacology and Experimental Therapeutics
-Aminoisobutyric Acid by Isolated
Perfused Rat Liver
1 Department of Pharmacology, Vanderbilt University, School of Medicine,
Nashville, Tennessee
In this study both hydrocortisone and insulin were shown to increase the uptake of
a nonmetabolizable amino acid,
-aminoisobutyric acid (AIB), by the isolated perfused rat liver. DNA-dependent RNA synthesis was inhibited by actinomycin D to
determine whether the effects of these hormones on transport were independent of
their actions on the transcription of genetic information. Actinomycin D inhibited enzyme
induction by hydrocortisone approximately 90% without affecting the increase in AIB
transport. However, approximately half of the insulin effect on AIB transport was
blocked by actinomycin D. The effect of hydrocortisone on the uptake of AIB was completely inhibited by phenoxybenzamine (PBZ), an adrenergic blocking agent. The action
of insulin on AIB uptake was not affected by PBZ. Hydrocortisone and insulin together
exerted an additive effect on the hepatic uptake of AIB. Both hormones act directly
(but apparently at different sites) to increase the AIB uptake by the liver. Most of
the steroid action and approximately half of the insulin action appears to be independent
of any effect these hormones have on DNA-dependent RNA synthesis in the liver.
Note:
ACKNOWLEDGMENTS
This work was supported, in part, by U.S.
Public Health Grant CA-02020 and, in part, by
U.S. Public Health Grant 2-RO1-AM-05474.
J. W. C., while a predoctoral trainee, was supported, in part, by U.S. Public Health Training
Grant 2-T1-GM-58 and, in part, by U.S. Public
Health Predoctoral Fellowship GFM-16,435.
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