TY - JOUR
T1 - Switching-on of serotonergic calcium signaling in activated hepatic stellate cells
AU - Park, Kyu Sang
AU - Sin, Pyo Jin
AU - Lee, Dong Hyeon
AU - Cha, Seung Kuy
AU - Kim, Min Jeong
AU - Kim, Na Hyun
AU - Baik, Soon Koo
AU - Jeong, Seong Woo
AU - Kong, In Deok
PY - 2011/1/14
Y1 - 2011/1/14
N2 - AIM: To investigate serotonergic Ca2+ signaling and the expression of 5-hydroxytryptamine (5-HT) receptors, as well as Ca2+ transporting proteins, in hepatic stellate cells (HSCs). METHODS: The intracellular Ca2+ concentration ([Ca2+]i) of isolated rat HSCs was measured with a fuorescence microscopic imaging system. Quantitative PCR was per-formed to determine the transcriptional levels of 5-HT receptors and endoplasmic reticulum (ER) proteins involved in Ca2+ storage and release in cultured rat HSCs. RESULTS: Distinct from quiescent cells, activated HSCs exhibited [Ca2+]i transients following treatment with 5-HT, which was abolished by U-73122, a phospholipase C inhibitor. Upregulation of 5-HT2A and 5-HT2B receptors, but not 5-HT3, was prominent during trans-differentiation of HSCs. Pretreatment with ritanserin, a 5-HT2 antagonist, inhibited [Ca2+]i changes upon application of 5-HT. Expression of type 1 inositol-5'-triphosphate receptor and type 2 sarcoplasmic/endoplasmic reticulum Ca2+ ATPase were also increased during activation of HSCs and serve as the major isotypes for ER Ca2+ storage and release in activated HSCs. Ca2+ binding chap-erone proteins of the ER, including calreticulin, calnexin and calsequestrin, were up-regulated following activation of HSCs. CONCLUSION: The appearance of 5-HT-induced [Ca2+]i response accompanied by upregulation of metabotropic 5-HT2 receptors and Ca2+ transporting/chaperone ER proteins may participate in the activating process of HSCs.
AB - AIM: To investigate serotonergic Ca2+ signaling and the expression of 5-hydroxytryptamine (5-HT) receptors, as well as Ca2+ transporting proteins, in hepatic stellate cells (HSCs). METHODS: The intracellular Ca2+ concentration ([Ca2+]i) of isolated rat HSCs was measured with a fuorescence microscopic imaging system. Quantitative PCR was per-formed to determine the transcriptional levels of 5-HT receptors and endoplasmic reticulum (ER) proteins involved in Ca2+ storage and release in cultured rat HSCs. RESULTS: Distinct from quiescent cells, activated HSCs exhibited [Ca2+]i transients following treatment with 5-HT, which was abolished by U-73122, a phospholipase C inhibitor. Upregulation of 5-HT2A and 5-HT2B receptors, but not 5-HT3, was prominent during trans-differentiation of HSCs. Pretreatment with ritanserin, a 5-HT2 antagonist, inhibited [Ca2+]i changes upon application of 5-HT. Expression of type 1 inositol-5'-triphosphate receptor and type 2 sarcoplasmic/endoplasmic reticulum Ca2+ ATPase were also increased during activation of HSCs and serve as the major isotypes for ER Ca2+ storage and release in activated HSCs. Ca2+ binding chap-erone proteins of the ER, including calreticulin, calnexin and calsequestrin, were up-regulated following activation of HSCs. CONCLUSION: The appearance of 5-HT-induced [Ca2+]i response accompanied by upregulation of metabotropic 5-HT2 receptors and Ca2+ transporting/chaperone ER proteins may participate in the activating process of HSCs.
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U2 - 10.3748/wjg.v17.i2.164
DO - 10.3748/wjg.v17.i2.164
M3 - Article
C2 - 21245988
AN - SCOPUS:79955778898
SN - 1007-9327
VL - 17
SP - 164
EP - 173
JO - World Journal of Gastroenterology
JF - World Journal of Gastroenterology
IS - 2
ER -