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Vildagliptin, an Anti-diabetic Drug of the DPP-4 Inhibitor, Induces Vasodilation via Kv Channel and SERCA Pump Activation in Aortic Smooth Muscle

  • Mi Seon Seo
  • Hongliang Li
  • Jin Ryeol An
  • In Duk Jung
  • Won-Kyo Jung
  • Kwon-Soo Ha
  • Eun-Taek Han
  • Seok-Ho Hong
  • Il-Whan Choi
  • Won Sun Park
Article
  • 16 Downloads

Abstract

This study investigated vildagliptin-induced vasodilation and its related mechanisms using phenylephrine induced precontracted rabbit aortic rings. Vildagliptin induced vasodilation in a concentration-dependent manner. Pretreatment with the large-conductance Ca2+-activated K+ channel blocker paxilline, ATP-sensitive K+ channel blocker glibenclamide, and inwardly rectifying K+ channel blocker Ba2+ did not affect the vasodilatory effects of vildagliptin. However, application of the voltage-dependent K+ (Kv) channel inhibitor 4-aminopyridine significantly reduced the vasodilatory effects of vildagliptin. In addition, application of either of two sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitors, thapsigargin or cyclopiazonic acid, effectively inhibited the vasodilatory effects of vildagliptin. These vasodilatory effects were not affected by pretreatment with adenylyl cyclase, protein kinase A (PKA), guanylyl cyclase, or protein kinase G (PKG) inhibitors, or by removal of the endothelium. From these results, we concluded that vildagliptin induced vasodilation via activation of Kv channels and the SERCA pump. However, other K+ channels, PKA/PKG-related signaling cascades associated with vascular dilation, and the endothelium were not involved in vildagliptin-induced vasodilation.

Keywords

Vildagliptin Voltage-dependent K+ channel SERCA pump Aortic smooth muscle 

Notes

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Education: 2016-R1D1A3B03930169) (Ministry of Science, ICT and Future Planning: 2015-R1A4A1038666).

Compliance with Ethical Standards

Conflict of interest

The authors declare that there are no conflicts of interest

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PhysiologyKangwon National University School of MedicineChuncheonSouth Korea
  2. 2.Laboratory of Dendritic Cell Differentiation and Regulation, Department of Immunology, School of MedicineKonkuk UniversityChungjuSouth Korea
  3. 3.Department of Biomedical Engineering, Center for Marine-Integrated Biomedical Technology (BK21 Plus)Pukyong National UniversityBusanSouth Korea
  4. 4.Department of Molecular and Cellular BiochemistryKangwon National University School of MedicineChuncheonSouth Korea
  5. 5.Department of Medical Environmental Biology and Tropical MedicineKangwon National University School of MedicineChuncheonSouth Korea
  6. 6.Department of Internal MedicineKangwon National University School of MedicineChuncheonSouth Korea
  7. 7.Department of Microbiology, College of MedicineInje UniversityBusanSouth Korea

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