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Anti-proliferating effect of iptakalim, a novel KATP channel opener, in cultured rabbit pulmonary arterial smooth muscle cells.
Eur J Pharmacol. 2005 Mar 28; 511(2-3):81-7.EJ

Abstract

ATP-sensitive potassium (K(ATP)) channels of pulmonary arterial smooth muscle cells (SMCs) have been implicated in pulmonary hypertension. Iptakalim, designed and synthesized by ourselves, is a newly selective K(ATP) channel opener. Here, we explored the effects of iptakalim on the rise of cytoplasmic free Ca(2+) concentration ([Ca(2+)](cyt)) induced by endothelin-1 (ET-1) and on the proliferation of cultured rabbit pulmonary arterial SMCs. The results showed that iptakalim inhibited the [Ca(2+)](cyt) increase. The enhanced [(3)H]thymidine incorporation was inhibited and the transition of cells from static phase (G(0)/G(1)) to DNA synthesis (S) and mitotic phase (G(2)/M) was held back by iptakalim in a concentration-dependent manner. Glyburide abolished the inhibitory effect of iptakalim. In conclusion, we have shown that iptakalim had an inhibitory effect on [Ca(2+)](cyt) increase and the proliferation of pulmonary arterial SMCs induced by endothelin-1 through activation of K(ATP) channels. These findings suggest that iptakalim might be a promising candidate for the treatment of pulmonary arterial remodeling in pulmonary hypertension.

Authors+Show Affiliations

Xie W
Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
Wang H
No affiliation info available
Ding J
No affiliation info available
Wang H
No affiliation info available
Hu G
No affiliation info available

MeSH

ATP-Binding Cassette TransportersAnimalsCalciumCell CycleCell ProliferationCells, CulturedDose-Response Relationship, DrugEndothelin-1KATP ChannelsMuscle, Smooth, VascularPotassium Channels, Inwardly RectifyingPropylaminesPulmonary ArteryRabbitsThymidine

Pub Type(s)

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

Language

eng

PubMed ID

15792775

Citation

Xie, Weiping, et al. "Anti-proliferating Effect of Iptakalim, a Novel KATP Channel Opener, in Cultured Rabbit Pulmonary Arterial Smooth Muscle Cells." European Journal of Pharmacology, vol. 511, no. 2-3, 2005, pp. 81-7.
Xie W, Wang H, Ding J, et al. Anti-proliferating effect of iptakalim, a novel KATP channel opener, in cultured rabbit pulmonary arterial smooth muscle cells. Eur J Pharmacol. 2005;511(2-3):81-7.
Xie, W., Wang, H., Ding, J., Wang, H., & Hu, G. (2005). Anti-proliferating effect of iptakalim, a novel KATP channel opener, in cultured rabbit pulmonary arterial smooth muscle cells. European Journal of Pharmacology, 511(2-3), 81-7.
Xie W, et al. Anti-proliferating Effect of Iptakalim, a Novel KATP Channel Opener, in Cultured Rabbit Pulmonary Arterial Smooth Muscle Cells. Eur J Pharmacol. 2005 Mar 28;511(2-3):81-7. PubMed PMID: 15792775.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-proliferating effect of iptakalim, a novel KATP channel opener, in cultured rabbit pulmonary arterial smooth muscle cells. AU - Xie,Weiping, AU - Wang,Hong, AU - Ding,Jianhua, AU - Wang,Hai, AU - Hu,Gang, PY - 2004/12/07/received PY - 2005/01/24/revised PY - 2005/01/28/accepted PY - 2005/3/29/pubmed PY - 2005/7/27/medline PY - 2005/3/29/entrez SP - 81 EP - 7 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 511 IS - 2-3 N2 - ATP-sensitive potassium (K(ATP)) channels of pulmonary arterial smooth muscle cells (SMCs) have been implicated in pulmonary hypertension. Iptakalim, designed and synthesized by ourselves, is a newly selective K(ATP) channel opener. Here, we explored the effects of iptakalim on the rise of cytoplasmic free Ca(2+) concentration ([Ca(2+)](cyt)) induced by endothelin-1 (ET-1) and on the proliferation of cultured rabbit pulmonary arterial SMCs. The results showed that iptakalim inhibited the [Ca(2+)](cyt) increase. The enhanced [(3)H]thymidine incorporation was inhibited and the transition of cells from static phase (G(0)/G(1)) to DNA synthesis (S) and mitotic phase (G(2)/M) was held back by iptakalim in a concentration-dependent manner. Glyburide abolished the inhibitory effect of iptakalim. In conclusion, we have shown that iptakalim had an inhibitory effect on [Ca(2+)](cyt) increase and the proliferation of pulmonary arterial SMCs induced by endothelin-1 through activation of K(ATP) channels. These findings suggest that iptakalim might be a promising candidate for the treatment of pulmonary arterial remodeling in pulmonary hypertension. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/15792775/Anti_proliferating_effect_of_iptakalim_a_novel_KATP_channel_opener_in_cultured_rabbit_pulmonary_arterial_smooth_muscle_cells_ DB - PRIME DP - Unbound Medicine ER -