December 1996

Glucagon Inhibits Hepatocyte Nitric Oxide Synthesis

Author Affiliations

From the Department of Surgery, University of Pittsburgh, Pittsburgh, Pa.

Arch Surg. 1996;131(12):1266-1272. doi:10.1001/archsurg.1996.01430240020002

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× 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