Affordable Access

Publisher Website

Iptakalim inhibited endothelin-1-induced proliferation of human pulmonary arterial smooth muscle cells through the activation of KATPchannel

Authors
Journal
Vascular Pharmacology
1537-1891
Publisher
Elsevier
Publication Date
Volume
48
Identifiers
DOI: 10.1016/j.vph.2008.01.001
Keywords
  • Atp-Sensitive K+Channels
  • Iptakalim
  • Endothelin-1
  • Human Pulmonary Arterial Smooth Muscle Cells
  • Mitogen-Activated Protein Kinases
Disciplines
  • Medicine

Abstract

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 Ca 2+ concentration ([Ca 2+] 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 [Ca 2+] 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.

There are no comments yet on this publication. Be the first to share your thoughts.