Feedback-inhibition of glucagon-stimulated glycogenolysis in hepatocyte/kupffer cell cocultures by glucagon-elicited prostaglandin production in kupffer cells

✍ Scribed by Ursula Hespeling; Kurt Jungermann; Gerhard P. Püschel

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 872 KB
• Volume: 22
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840220534

✦ Synopsis

Prostaglandins, released from Kupffer cells, have been shown to mediate the increase in hepatic glycogenolysis by various stimuli such as zymosan, endotoxin, immune complexes, and anaphylotoxin C3a involving prostaglandin (PG) receptors coupled to phospholipase C via a Go protein. PGs also decreased glucagon-stimulated glycogenolysis in hepatocytes by a different signal chain involving PGE, receptors coupled to adenylate cyclase via a Gi protein (EP3 receptors). The source of the prostaglandins for this latter glucagon-antagonistic action is so far unknown. This study provides evidence that Kupffer cells may be one source: in Kupffer cells, maintained in primary culture for 72 hours, glucagon (0.1 to 10 moll L) increased PGE,, PGF,,, and PGD, synthesis rapidly and transiently. Maximal prostaglandin concentrations were reached after 5 minutes. Glucagon (1 nmovL) elevated the cyclic adenosine monophosphate (CAMP) and inositol triphosphate (InsP,) levels in Kupffer cells about fivefold and twofold, respectively. The increase in glycogen phosphorylase activity elicited by l nmol/L glucagon was about twice as large in monocultures of hepatocytes than in cocultures of hepatocytes and Kupffer ceUs with the same hepatocyte density. Treatment of cocultures with 500 pmoVL acetylsalicylic acid (MA) to irreversibly inhibit cyclooqgenase (PGH-synthase) 30 minutes before addition of glucagon abolished this difference. These data support the hypothesis that PGs produced by Kupffer cells in response to glucagon might participate in a feedback loop inhibiting glucagon-stimulated glycogenolysis in hepatocytes.