Effects of ATP-sensitive potassium channel openers on the contractile and phosphatidylinositol responses of the rat trachea

Maeda, Shiro; Shibata, Osamu; Saito, Masataka; Tsuda, Atsushi; Shibata, Shinichi; Makita, Tetsuji; Sumikawa, Koji

doi:10.1007/s005400200043

Cited by 2 publications

(2 citation statements)

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“…Moreover, since agents that suppress potassium permeability (4-aminopyridien, procaine, and TEA) reduced both the hyperpolarization and the relaxation, the opening of plasmalemmal K + channels was proposed as the mechanism; but no particular K + channel was designated. Further, cromakalim plus a second K ATP channel opener, Y-26763, have been shown to reduce the tension of a carbachol-induced contraction of the rat trachea [23]. In isolated human ASM cells, however, the K ATP channel opener, pinacidil, but not cromakalim or diazoxide, effectively relaxed ASM (Figure 3A,B).…”

Section: Discussionmentioning

confidence: 99%

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H2S relaxes isolated human airway smooth muscle cells via the sarcolemmal KATP channel

Fitzgerald

DeSantiago

Lee

et al. 2014

Biochemical and Biophysical Research Communications

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Here we explored the impact of hydrogen sulfide (H2S) on biophysical properties of the primary human airway smooth muscle (ASM)–the end effector of acute airway narrowing in asthma. Using Magnetic Twisting Cytometry (MTC), we measured dynamic changes in the stiffness of isolated ASM, at the single-cell level, in response to varying doses of GYY4137 (1–10 mM). GYY4137 slowly released appreciable levels of H2S in the range of 10–275 µM, and H2S released was long lived. In isolated human ASM cells, GYY4137 acutely decreased stiffness (i.e. an indicator of the single-cell relaxation) in a dose-dependent fashion, and stiffness decreases were sustained in culture for 24h. Human ASM cells showed protein expressions of cystathionine-γ-lyase (CSE; a H2S synthesizing enzyme) and ATP-sensitive potassium (KATP) channels. The KATP channel opener pinacidil effectively relaxed isolated ASM cells. In addition, pinacidil-induced ASM relaxation was completely inhibited by the treatment of cells with the KATP channel blocker glibenclamide. Glibenclamide also markedly attenuated GYY4137-mediated relaxation of isolated human ASM cells. Taken together, our findings demonstrate that H2S causes the relaxation of human ASM and implicate as well the role for sarcolemmal KATP channels. Finally, given that ASM cells express intrinsic enzymatic machinery of generating H2S, we suggest thereby this class of gasotransmitter can be further exploited for potential therapy against obstructive lung disease.

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Section: Discussionmentioning

confidence: 99%

“…Few studies have focused on the mechanistic actions of H 2 S in the lung-resident cells. Even though the role of K ATP channels in regulating airway functions has been reported [21; 22; 23], the effects of H 2 S on airway smooth muscle (ASM), the end-effector of acute airway narrowing, are largely unexplored.…”

Section: Introductionmentioning

confidence: 99%