Glucagon inhibits hepatocyte nitric oxide synthesis

Archives of Surgery
B G HarbrechtT R Billiar

Abstract

To investigate the effects of glucagon on nitric oxide (NO) synthesis in cultured rat hepatocytes. Laboratory. Male Sprague-Dawley rats (weight, 200-250 g). 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 22536 (from 10(-5) to 10(-3) mol/L). 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. 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 22536 restored glucagon-induced decreases in NO synthesis. 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.

Citations

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