Glucagon inhibits hepatocyte nitric oxide synthesis.
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.
Harbrecht
B G
BG
Department of Surgery, University of Pittsburgh, Pa, USA.
Wirant
E M
EM
Kim
Y M
YM
Billiar
T R
TR
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
D005765:Gastrointestinal Agents; D007375:Interleukin-1; D012333:RNA, Messenger; D009569:Nitric Oxide; D005934:Glucagon; D019001:Nitric Oxide Synthase