Effects of octreotide on expression of L-type voltage-operated calcium channels and on intracellular Ca2+ in activated hepatic stellate cells.
BACKGROUND
The contractility of hepatic stellate cells (HSCs) may play an important role in the pathogenesis of cirrhosis with portal hypertension. The aim of this study was to research the effects of octreotide, an analogue of somatostatin, on intracellular Ca2+ and on the expression of L-type voltage-operated calcium channels (L-VOCCs) in activated HSCs, and to try to survey the use of octreotide in treatment and prevention of cirrhosis with portal hypertension complications.


METHODS
HSC-T6, an activated HSCs line, was plated on small glass coverslips in 35-mm culture dishes at a density of 1 x 10(5)/ml, and incubated in DMEM media for 24 hours. After the cells were loaded with Fluo-3/AM, intracellular Ca2+ was measured by Laser Scanning Confocal Microscopy (LSCM). The dynamic changes in activated HSCs of intracellular Ca2+, stimulated by octreotide, endothelin-1, and KCl, respectively, were also determined by LSCM. Each experiment was repeated six times. L-VOCC expression in HSCs was estimated by immunocytochemistry.


RESULTS
After octreotide stimulation, a significant decrease in the intracellular Ca2+ of activated HSCs was observed. However, octreotide did not inhibit the increases in intracellular Ca2+ after stimulation by KCl and endothelin-1. Moreover, octreotide did not significantly affect L-VOCC expression. These results suggest that neither L-VOCC nor endothelin-1 receptors in activated HSCs are inhibited by octreotide.


CONCLUSIONS
Octreotide may decrease portal hypertension and intrahepatic vascular tension by inhibiting activated HSCs contractility through decreases in intracellular Ca2+. The somatostatin receptors in activated HSCs may be inhibited by octreotide.
Ding
Hui-guo
HG
Department of GI & Hepatology, Capital University of Medical Sciences, Beijing You An Hospital, Beijing 100054, China. Dinghg3079_cn@sina.com
Wang
Bao-en
BE
Jia
Ji-dong
JD
Xia
Hua-xiang Harry
HX
Wong
Chun-yu Benjamin
CY
Zhao
Chun-hui
CH
Xu
Yan-lin
YL
D002118:Calcium / Q000032:analysis*; D020746:Calcium Channels, L-Type / Q000032:analysis*; D002478:Cells, Cultured; D022781:Hepatocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D018613:Microscopy, Confocal; D015282:Octreotide / Q000494:pharmacology*
D020746:Calcium Channels, L-Type; D015282:Octreotide; D002118:Calcium