| Autor: |
C R, Gandhi, T, Uemura, R, Kuddus |
| Rok vydání: |
2000 |
| Předmět: |
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| Zdroj: |
British journal of pharmacology. 131(2) |
| ISSN: |
0007-1188 |
| Popis: |
Hepatic stellate cells (HSC) and their transformed phenotype found in the chronically injured liver play important roles in hepatic physiology and pathology. HSC produce and react to a potent contractile peptide endothelin-1 (ET-1) and also synthesize a vasorelaxant nitric oxide (NO) upon stimulation with endotoxin. However, whether endotoxin affects ET-1 system of HSC and if this is a mechanism of endotoxin-induced hepatic injury is not known. We characterized synthesis of ET-1 and NO and ET-1 receptors in cultured quiescent and transformed HSC subjected to endotoxin treatment. Endotoxin (1 - 1000 ng ml(-1)) stimulated synthesis of ET-1 and NO and up-regulated ET-1 receptors in both cell types. Inhibition of NO synthesis by N(G)-monomethyl-L-homoarginine strongly inhibited endotoxin-induced increase in ET-1 receptors in transformed HSC but produced small additional increase in quiescent HSC. Inhibition of soluble guanylyl cyclase by 1H-[1,2, 4]oxadiazolo[4,3-a]quinoxalin-1-one blocked the effect of endotoxin on ET-1 receptors in both cell types. Moreover, ET-1 receptors were increased in both cell types during earlier time points (1 - 4 h) of endotoxin treatment in the absence of the stimulation of NO synthesis. These results demonstrate that endotoxin up-regulates ET-1 receptors in HSC by NO-dependent and -independent mechanisms. Such effects of endotoxin can be of importance in acute endotoxemia and during chronic injury of the liver. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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