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 22536 (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 22536 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.
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 22536 (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 22536 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.
Authors: Baochun Zhang; Will Crankshaw; Ryan Nesemeier; Jay Patel; Ikenna Nweze; Jaganathan Lakshmanan; Brian G Harbrecht Journal: J Surg Res Date: 2014-07-24 Impact factor: 2.192
Authors: Brian G Harbrecht; Ikenna Nweze; Jason W Smith; Baochun Zhang Journal: Am J Physiol Gastrointest Liver Physiol Date: 2011-10-28 Impact factor: 4.052
Authors: Ikenna C Nweze; Jason W Smith; Baochun Zhang; Carolyn M Klinge; Jaganathan Lakshmanan; Brian G Harbrecht Journal: J Trauma Acute Care Surg Date: 2012-08 Impact factor: 3.313