Riko Miyaki, Aya Yamamura, Akiko Kawade, Moe Fujiwara, Rubii Kondo, Yoshiaki Suzuki, Hisao Yamamura
Biochemical and biophysical research communications 2022 Jun 04In 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. Copyright © 2022 Elsevier Inc. All rights reserved.
Riko Miyaki, Aya Yamamura, Akiko Kawade, Moe Fujiwara, Rubii Kondo, Yoshiaki Suzuki, Hisao Yamamura. SKF96365 activates calcium-sensing receptors in pulmonary arterial smooth muscle cells. Biochemical and biophysical research communications. 2022 Jun 04;607:44-48
PMID: 35366542
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