title: Glucagon inhibits hepatocyte nitric oxide synthesis.
abstract: OBJECTIVE
  To investigate the effects of glucagon on nitric oxide (NO) synthesis in cultured rat hepatocytes.
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  Male Sprague-Dawley rats (weight, 200-250 g).
  
  
  METHODS
  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).
  
  
  METHODS
  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.affiliation: Department of Surgery, University of Pittsburgh, Pa, USA.
authors.forename: B G
authors.initials: BG
authors.lastname: Harbrecht
authors.forename: E M
authors.initials: EM
authors.lastname: Wirant
authors.forename: Y M
authors.initials: YM
authors.lastname: Kim
authors.forename: T R
authors.initials: TR
authors.lastname: Billiar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D005765:Gastrointestinal Agents; D007375:Interleukin-1; D012333:RNA, Messenger; D009569:Nitric Oxide; D005934:Glucagon; D019001:Nitric Oxide Synthase