Glucagon Inhibits Hepatocyte Nitric Oxide Synthesis
Brian G. Harbrecht, MD;
Elizabeth M. Wirant;
Young-Myeong Kim, PhD;
Timothy R. Billiar, MD
Arch Surg. 1996;131(12):1266-1272.
Abstract
Objective
To investigate the effects of glucagon on nitric oxide (NO) synthesis in cultured rat hepatocytes.
Setting
Laboratory.
Materials
Male Sprague-Dawley rats (weight, 200-250 g).
Interventions
Isolated rat hepatocytes were cultured with interleukin-1 to stimulate NO synthesis. Glucagon was added at increasing concentrations (from 10–9 to 2x 10–5 mol/L) at the time of interleukin-1 stimulation. Selected cultures were treated with the adenylate cyclase inhibitor, SQ 22 536 (from 10–5 to 10–3 mol/L).
Main Outcome Measures
Nitric oxide synthesis was assessed by measuring the concentrations of culture supernatant nitrite and nitrite plus nitrate, hepatocyte nitric oxide synthase-2 (NOS-2) messenger RNA (mRNA), and NOS-2 protein.
Results
Interleukin-1 stimulated hepatocyte NO synthesis, and this synthesis was inhibited by glucagon in a dose-dependent manner. Glucagon inhibited the accumulation of supernatant nitrite and the expression of NOS-2 mRNA and NOS-2 protein. SQ 22 536 restored glucagon-induced decreases in NO synthesis.
Conclusions
Glucagon inhibits NO synthesis in interleukin-1–stimulated hepatocytes in vitro. This inhibition seems to be mediated by glucagon-induced changes in cyclic adenosine monophosphate.
Arch Surg. 1996;131:1266-1272
Author Affiliations
From the Department of Surgery, University of Pittsburgh, Pittsburgh, Pa.
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