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- W4220909045 abstract "In pulmonary arterial smooth muscle cells (PASMCs), an increase in the cytosolic Ca2+ concentration ([Ca2+]cyt) is involved in many physiological processes such as cell contraction and proliferation. However, chronic [Ca2+]cyt increases cause pulmonary vasoconstriction and vascular remodeling, resulting in pulmonary arterial hypertension (PAH). Therefore, [Ca2+]cyt signaling plays a substantial role in the regulation of physiological and pathological functions in PASMCs. In the present study, the effects of SKF96365 on [Ca2+]cyt were examined in PASMCs from normal subjects and idiopathic pulmonary arterial hypertension (IPAH) patients. SKF96365 is widely used as a blocker of non-selective cation channels. SKF96365 did not affect the resting [Ca2+]cyt in normal-PASMCs. However, SKF96365 increased [Ca2+]cyt in IPAH-PASMCs in a concentration-dependent manner (EC50 = 18 μM). The expression of Ca2+-sensing receptors (CaSRs) was higher in IPAH-PASMCs than in normal-PASMCs. The SKF96365-induced [Ca2+]cyt increase was inhibited by CaSR antagonists, NPS2143 and Calhex 231. The CaSR-mediated [Ca2+]cyt increase was facilitated by SKF96365 and the activation was blocked by NPS2143 or Calhex 231. In addition, the SKF96365-induced [Ca2+]cyt increase was reduced by siRNA knockdown of CaSRs. Taken together, SKF96365 activates CaSRs in IPAH-PASMCs and promotes [Ca2+]cyt signaling." @default.
- W4220909045 created "2022-04-03" @default.
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- W4220909045 date "2022-06-01" @default.
- W4220909045 modified "2023-09-30" @default.
- W4220909045 title "SKF96365 activates calcium-sensing receptors in pulmonary arterial smooth muscle cells" @default.
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- W4220909045 doi "https://doi.org/10.1016/j.bbrc.2022.03.121" @default.
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