Stimulation by anaphylatoxin C5a of glycogen phosphorylase in rat hepatocytes via prostanoid release from hepatic stellate cells but not sinusoidal endothelial cells.
In the perfused rat liver, the anaphylatoxin C5a has been shown to enhance glucose output. Since hepatocytes lack C5a receptor mRNA, the metabolic effect of C5a must be elicited indirectly via C5a receptor expressing non-parenchymal liver cells. Kupffer cells were found to be able to mediate the C5a action via release of prostanoids. However, elimination of the Kupffer cells by pretreatment of the animals with gadolinium chloride reduced the metabolic effect of C5a to only about 40%. Therefore, it was investigated whether not only Kupffer cells but in addition also hepatic stellate cells or sinusoidal endothelial cells released prostanoids in response to C5a. In isolated hepatic stellate cells but not in sinusoidal endothelial cells, recombinant rat C5a induced a time- and dose-dependent release of thromboxane B2 and prostaglandins D2, E2 and F2alpha. The rate of prostanoid release was maximal within the first two minutes and then declined again. C5a-induced prostanoid release from hepatic stellate cells was smaller than that from Kupffer cells and it differed in the prostanoid ratios (PGE2/PGD2/PGF2alpha/TXB2 = 1:1:0.1:0.6 and 1:4:1:3, respectively). RrC5a activated hepatocellular glycogen phosphorylase via prostanoid release in cocultures of hepatocytes with hepatic stellate cells but not with sinusoidal endothelial cells. Thus, the part of the rrC5a-induced glucose output in the perfused rat liver, which was not abrogated by elimination of the Kupffer cells with gadolinium chloride, most likely was mediated by prostanoids released from hepatic stellate cells.
Schieferdecker
H L
HL
Institut für Biochemie und Molekulare Zellbiologie, Georg-August-Universität Göttingen, Germany. hschief@gwdg.de
Pestel
S
S
Rothermel
E
E
Püschel
G P
GP
Götze
O
O
Jungermann
K
K
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D015936:Complement C5a / Q000378:metabolism / Q000494:pharmacology*; D004789:Enzyme Activation; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D006005:Phosphorylases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D011453:Prostaglandins; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D015936:Complement C5a; D006005:Phosphorylases