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 fluorescence microscopic imaging system. Quantitative PCR was performed 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-HT(2A) and 5-HT(2B) 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 chaperone 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020369 | PMC |
| http://dx.doi.org/10.3748/wjg.v17.i2.164 | DOI Listing |
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