Somatostatin suppresses endothelin-1-induced rat hepatic stellate cell contraction via somatostatin receptor subtype 1.
OBJECTIVE
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.
Reynaert
H
H
Laboratory for Molecular Liver Cell Biology, Free University of Brussels (VUB), Belgium. Hendrik.Reynaert@az.vub.ac.be
Vaeyens
F
F
Qin
H
H
Hellemans
K
K
Chatterjee
N
N
Winand
D
D
Quartier
E
E
Schuit
F
F
Urbain
D
D
Kumar
U
U
Patel
Y C
YC
Geerts
A
A
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D017931:DNA Primers; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000494:pharmacology*; D014158:Transcription, Genetic
D017931:DNA Primers; D019332:Endothelin-1; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; D013004:Somatostatin