Switching-on of serotonergic calcium signaling in activated hepatic stellate cells

Kyu Sang Park, Pyo Jin Sin, Dong Hyeon Lee, Seung Kuy Cha, Min Jeong Kim, Na Hyun Kim, Soon Koo Baik, Seong Woo Jeong, In Deok Kong

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5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)164-173
Number of pages10
JournalWorld Journal of Gastroenterology
Volume17
Issue number2
DOIs
Publication statusPublished - 2011 Jan 14

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All Science Journal Classification (ASJC) codes

  • Gastroenterology

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