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Reynaert, H. et al.

Reynaert, Vaeyens, Qin, Hellemans, Chatterjee, Winand, Quartier, Schuit, Urbain, Kumar, Patel, Geerts,

Somatostatin suppresses endothelin-1- induced rat hepatic stellate cell contraction via somatostatin receptor subtype 1.

BACKGROUND & AIMS: Hepatic stellate cells (HSCs) are considered therapeutic targets to decrease portal hypertension. To elucidate some of the hemodynamic effects of somatostatin ( SST) on portal pressure, the presence and function of SST receptors (SSTRs) on HSCs were investigated. METHODS: SSTR messenger RNA expression, and SSTR presence was investigated using reverse-transcription polymerase chain reaction, real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. The function of SSTRs was studied by examining the effects of SST and specific SSTR agonists on endothelin-1(ET-1)-induced HSC contraction. RESULTS: Specific amplicons for SSTR subtypes 1, 2, and 3 were demonstrated in rat liver and in activated HSCs. The presence of SSTR subtypes 1, 2, and 3 was confirmed by Western blotting. With immunohistochemistry, a strong staining of HSCs was obtained for SSTR subtypes 1, 2, and 3 in CCl4-treated rats, but not in normal rat liver. Incubation of HSCs on collagen gels with buffer, 10(-8) mol/L SST, and 2 x 10(-8) mol/L ET-1 resulted in collagen surface area decreases of 5.5% +/- 3.3%, 6.8% +/- 4.4%, and 49.8% +/- 8.3%, respectively. Relative contraction of gels preincubated with 10(-8) mol/L SST followed by 2 x 10(-8) mol/L ET-1 or vice versa as compared with maximal contraction (100%) with 2 x 10(-8) mol/L ET-1 were 72.6% +/- 17.9% and 76.2% +/- 12.6%, respectively (P < 0.05). SSTR agonist 1, but not SSTR agonist 2 or 3, was able to counteract the contractile effect of ET-1. CONCLUSIONA: Activated rat HSCs bear SSTR subtypes 1, 2, and 3. SST causes significant partial inhibition of ET-1-induced contraction of activated HSCs, mainly by stimulation of SSTR subtype 1.[1]

References

Somatostatin suppresses endothelin-1-induced rat hepatic stellate cell contraction via somatostatin receptor subtype 1. Reynaert, H., Vaeyens, F., Qin, H., Hellemans, K., Chatterjee, N., Winand, D., Quartier, E., Schuit, F., Urbain, D., Kumar, U., Patel, Y.C., Geerts, A. Gastroenterology (2001) [Pubmed]

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