Page 4 - Y. Vascular biology

[Y. Vascular biology-3]

The vasodilatory effect of gemigliptin via activation of

voltage-dependent K+ channels and SERCA pumps in aortic

smooth muscle

Hee Seok Jung¹, Won Sun Park¹

¹Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, South Korea

This study investigated the vasodilatory effects and acting mechanism of gemigliptin, a dipeptidyl peptidase-4 (DPP-
4) inhibitor. Tests were conducted in aortic rings pre-contracted with phenylephrine. Gemigliptin induced dose-
dependent vasodilation of the aortic smooth muscle. Several pre-treatment groups were used to investigate the

mechanism of action. While pre-treatment with large-conductance Ca2+-activated K+ channel inhibitor, ATP-
sensitive K+ channel inhibitor, and inwardly rectifying K+ channel inhibitor, had no impact on the vasodilatory effect

of gemigliptin, pre-treatment with voltage-dependent K+ (Kv) channel inhibitor, effectively attenuated the
vasodilatory action of gemigliptin. In addition, pre-treatment with thapsigargin, SERCA pump inhibitor, significantly

reduced the vasodilatory effect of gemigliptin. cAMP/PKA-related or cGMP/PKG-related signaling pathway inhibitors
did not alter the vasodilatory effect of gemigliptin. Similarly, elimination of the endothelium and pre-treatment with

a NO synthase inhibitor did not change the gemigliptin effect. These findings suggested that gemigliptin induces
vasodilation through the activation of Kv channels and SERCA pumps independent of cAMP/PKA-related or

cGMP/PKG-related signaling pathways and the endothelium.