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Iptakalim inhibited endothelin-1-induced proliferation of human pulmonary arterial smooth muscle cells through the activation of K(ATP) channel.
Vascul Pharmacol. 2008 Feb-Mar; 48(2-3):92-9.VP

Abstract

To determine whether iptakalim inhibited endothelin-1(ET-1)-induced proliferation of human pulmonary arterial smooth muscle cells (PASMCs) through the activation of ATP-sensitive potassium (K(ATP)) channel, the effect of iptakalim on the ET-1-induced proliferation of human PASMCs was examined by [3H]thymidine incorporation, staining with propidium iodide and flow cytometry analyses, measurement of cytosolic free Ca2+ concentration ([Ca2+]cyt) and Western blot for the phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in vitro. The results showed that iptakalim inhibited the ET-1-induced proliferation of human PASMCs, including [3H]thymidine incorporation and the transition of cell cycle phase, and blocked the ET-1-induced transient raise of [Ca2+]cyt, and the ET-1-induced phosphorylation of ERK1/2 in the human PASMCs. Iptakalim exerted a similar role as pinacidil did in human PASMCs and both inhibited the [3H] thymidine incorporation and the transition of cell cycle phase induced by ET-1 in the human PASMCs. Furthermore, we found that the inhibition of iptakalim and pinacidil on the ET-1-induced proliferation of human PASMCs was blocked by glyburide, a selective K(ATP) channel antagonist. These findings provide a strong evidence to support that iptakalim acts as a specific K(ATP) channel opener to antagonize the proliferating effect of ET-1 in the human PASMCs. This study provides further evidence that iptakalim may serve as another candidate drug to treat pulmonary hypertension.

Authors+Show Affiliations

Department of Respiratory Medicine, the First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18276195

Citation

Zhu, Yuming, et al. "Iptakalim Inhibited Endothelin-1-induced Proliferation of Human Pulmonary Arterial Smooth Muscle Cells Through the Activation of K(ATP) Channel." Vascular Pharmacology, vol. 48, no. 2-3, 2008, pp. 92-9.
Zhu Y, Zhang S, Xie W, et al. Iptakalim inhibited endothelin-1-induced proliferation of human pulmonary arterial smooth muscle cells through the activation of K(ATP) channel. Vascul Pharmacol. 2008;48(2-3):92-9.
Zhu, Y., Zhang, S., Xie, W., Li, Q., Zhou, Y., & Wang, H. (2008). Iptakalim inhibited endothelin-1-induced proliferation of human pulmonary arterial smooth muscle cells through the activation of K(ATP) channel. Vascular Pharmacology, 48(2-3), 92-9. https://doi.org/10.1016/j.vph.2008.01.001
Zhu Y, et al. Iptakalim Inhibited Endothelin-1-induced Proliferation of Human Pulmonary Arterial Smooth Muscle Cells Through the Activation of K(ATP) Channel. Vascul Pharmacol. 2008 Feb-Mar;48(2-3):92-9. PubMed PMID: 18276195.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Iptakalim inhibited endothelin-1-induced proliferation of human pulmonary arterial smooth muscle cells through the activation of K(ATP) channel. AU - Zhu,Yuming, AU - Zhang,Shijiang, AU - Xie,Weiping, AU - Li,Qingling, AU - Zhou,Yanjuan, AU - Wang,Hong, Y1 - 2008/01/16/ PY - 2007/07/28/received PY - 2007/12/15/revised PY - 2008/01/04/accepted PY - 2008/2/16/pubmed PY - 2008/7/29/medline PY - 2008/2/16/entrez SP - 92 EP - 9 JF - Vascular pharmacology JO - Vascul Pharmacol VL - 48 IS - 2-3 N2 - To determine whether iptakalim inhibited endothelin-1(ET-1)-induced proliferation of human pulmonary arterial smooth muscle cells (PASMCs) through the activation of ATP-sensitive potassium (K(ATP)) channel, the effect of iptakalim on the ET-1-induced proliferation of human PASMCs was examined by [3H]thymidine incorporation, staining with propidium iodide and flow cytometry analyses, measurement of cytosolic free Ca2+ concentration ([Ca2+]cyt) and Western blot for the phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in vitro. The results showed that iptakalim inhibited the ET-1-induced proliferation of human PASMCs, including [3H]thymidine incorporation and the transition of cell cycle phase, and blocked the ET-1-induced transient raise of [Ca2+]cyt, and the ET-1-induced phosphorylation of ERK1/2 in the human PASMCs. Iptakalim exerted a similar role as pinacidil did in human PASMCs and both inhibited the [3H] thymidine incorporation and the transition of cell cycle phase induced by ET-1 in the human PASMCs. Furthermore, we found that the inhibition of iptakalim and pinacidil on the ET-1-induced proliferation of human PASMCs was blocked by glyburide, a selective K(ATP) channel antagonist. These findings provide a strong evidence to support that iptakalim acts as a specific K(ATP) channel opener to antagonize the proliferating effect of ET-1 in the human PASMCs. This study provides further evidence that iptakalim may serve as another candidate drug to treat pulmonary hypertension. SN - 1537-1891 UR - https://www.unboundmedicine.com/medline/citation/18276195/Iptakalim_inhibited_endothelin_1_induced_proliferation_of_human_pulmonary_arterial_smooth_muscle_cells_through_the_activation_of_K_ATP__channel_ DB - PRIME DP - Unbound Medicine ER -