Glucagon inhibits hepatocyte nitric oxide synthesis

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

doi:10.1001/archsurg.1996.01430240020002

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 journal › Article › peer-review

26 Scopus citations

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 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 language	English
Pages (from-to)	1266-1272
Number of pages	7
Journal	Archives of Surgery
Volume	131
Issue number	12
DOIs	https://doi.org/10.1001/archsurg.1996.01430240020002
State	Published - Dec 1996
Externally published	Yes

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10.1001/archsurg.1996.01430240020002

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@article{0bb76f839546454b97212cc551272531,

title = "Glucagon inhibits hepatocyte nitric oxide synthesis",

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 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.",

author = "Harbrecht, {Brian G.} and Wirant, {Elizabeth M.} and Kim, {Yoimg Myeong} and Billiar, {Timothy R.}",

note = "Funding Information: This study was supported by grant GM-44100 from the ofHealth, Bethesda, (Dr Billiar). NationalInstitutesrecipientof George Md MemorialCareerDevelopmentAwardoftheAmericanCol¬ lege ofSurgeons, Chicago, 111. Presentedatthe16thAnnualMeetingoftheSurgi¬ cal Infection Society, Milwaukee, Wis, April 25, 1996. DNAwasmacrophageCharlescomplemen¬ tary provided by J. Baltimore,Md. Lowenstein,MD, Correspondingauthor:BrianG.Harbrecht,MD,A1010 PresbyterianUniversityHospital, St, burgh,PA15213.",

year = "1996",

month = dec,

doi = "10.1001/archsurg.1996.01430240020002",

language = "English",

volume = "131",

pages = "1266--1272",

journal = "Archives of Surgery",

issn = "0004-0010",

number = "12",

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TY - JOUR

T1 - Glucagon inhibits hepatocyte nitric oxide synthesis

AU - Harbrecht, Brian G.

AU - Wirant, Elizabeth M.

AU - Kim, Yoimg Myeong

AU - Billiar, Timothy R.

N1 - Funding Information: This study was supported by grant GM-44100 from the ofHealth, Bethesda, (Dr Billiar). NationalInstitutesrecipientof George Md MemorialCareerDevelopmentAwardoftheAmericanCol¬ lege ofSurgeons, Chicago, 111. Presentedatthe16thAnnualMeetingoftheSurgi¬ cal Infection Society, Milwaukee, Wis, April 25, 1996. DNAwasmacrophageCharlescomplemen¬ tary provided by J. Baltimore,Md. Lowenstein,MD, Correspondingauthor:BrianG.Harbrecht,MD,A1010 PresbyterianUniversityHospital, St, burgh,PA15213.

PY - 1996/12

Y1 - 1996/12

N2 - 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.

AB - 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.

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U2 - 10.1001/archsurg.1996.01430240020002

DO - 10.1001/archsurg.1996.01430240020002

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SN - 0004-0010

VL - 131

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JO - Archives of Surgery

JF - Archives of Surgery

IS - 12

ER -

Glucagon inhibits hepatocyte nitric oxide synthesis

Abstract

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