Glucagon inhibits hepatocyte nitric oxide synthesis

Brian G. Harbrecht*, Elizabeth M. Wirant, Yoimg Myeong Kim, Timothy R. Billiar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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 2 x 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.

Original languageEnglish
Pages (from-to)1266-1272
Number of pages7
JournalArchives of Surgery
Issue number12
StatePublished - Dec 1996
Externally publishedYes


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