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 hemodyna mic effects of somatostatin (SST) on portal pressure, the presence and func tion of SST receptors (SSTRs) on HSCs were investigated. Methods: SSTR mess enger RNA expression, and SSTR presence was investigated using reverse-tran scription polymerase chain reaction, real-time quantitative polymerase chai n reaction, Western blotting, and immunohistochemistry. The function of SST Rs was studied by examining the effects of SST and specific SSTR agonists o n endothelin-1(ET-1)-induced HSC contraction. Results: Specific amplicons f or SSTR subtypes 1, 2, and 3 were demonstrated in rat liver and in activate d 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, a nd 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 contr action of gels preincubated with 10(-8) mol/L SST followed by 2 X 10(-8) mo l/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 counterac t the contractile effect of ET-1. Conclusions. Activated rat HSCs bear SSTR subtypes 1, 2, and 3. SST causes significant partial inhibition of ET-1-in duced contraction of activated HSCs, mainly by stimulation of SSTR subtype 1.