Multiple regulatory actions of 2-guanidine-4-methylquinazoline (GMQ), an agonist of acid-sensing ion channel type 3, on ionic currents in pituitary GH 3 cells and in olfactory sensory (Rolf B1.T) neurons

Edmund Cheung So, Yingwei Wang, Li Qun Yang, Kenny Hsu So, Yi Ching Lo, Sheng-Nan Wu

研究成果: Article

4 引文 (Scopus)

摘要

GMQ (2-guanidine-4-methylquinazoline or N-(4-methyl-2-quinazolinyl)-guanidine hydrochloride), an agonist of acid-sensing ion channel type 3, has been increasingly used for in vivo studies of alternations in nociceptic behavior. In this study, we tried to investigate whether GMQ has any possible effect on other types of ion channels. Addition of GMQ to pituitary GH3 cells raised the amplitude of Ca 2+ -activated K + currents (I K(Ca) ), which was reversed by verruculogen or PF1022A, but not by TRAM-39. Under inside-out current recordings, addition of GMQ into bath enhanced the probability of large-conductance Ca 2+ -activated K + (BK Ca ) channels with an EC 50 value of 0.95 µM. The activation curve of BK Ca channels during exposure to GMQ shifted to a lower depolarized potential, with no change in the gating charge of the curve; however, there was a reduction of free energy for channel activation in its presence. As cells were exposed to GMQ, the amplitude of ion currents were suppressed, including delayed rectifying K + current, voltage-gated Na + and L-type Ca 2+ currents. In Rolf B1.T olfactory sensory neuron, addition of GMQ was able to induce inward current and to suppress peak I Na . Taken together, findings from these results indicated that in addition to the activation of ASIC3 channels, this compound might directly produce additional actions on various types of ion channels. Caution should be taken in the interpretation of in vivo experimental results when GMQ or other structurally similar compounds are used as targets to characterize the potential functions of ASIC3 channels.

原文English
頁(從 - 到)79-88
頁數10
期刊Biochemical Pharmacology
151
DOIs
出版狀態Published - 2018 五月 1

指紋

Acid Sensing Ion Channels
Somatotrophs
Neurons
Large-Conductance Calcium-Activated Potassium Channels
Chemical activation
Ion Channels
Olfactory Receptor Neurons
2-guanidine-4-methylquinazoline
Guanidine
Baths
Free energy
Ions

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

引用此文

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title = "Multiple regulatory actions of 2-guanidine-4-methylquinazoline (GMQ), an agonist of acid-sensing ion channel type 3, on ionic currents in pituitary GH 3 cells and in olfactory sensory (Rolf B1.T) neurons",
abstract = "GMQ (2-guanidine-4-methylquinazoline or N-(4-methyl-2-quinazolinyl)-guanidine hydrochloride), an agonist of acid-sensing ion channel type 3, has been increasingly used for in vivo studies of alternations in nociceptic behavior. In this study, we tried to investigate whether GMQ has any possible effect on other types of ion channels. Addition of GMQ to pituitary GH3 cells raised the amplitude of Ca 2+ -activated K + currents (I K(Ca) ), which was reversed by verruculogen or PF1022A, but not by TRAM-39. Under inside-out current recordings, addition of GMQ into bath enhanced the probability of large-conductance Ca 2+ -activated K + (BK Ca ) channels with an EC 50 value of 0.95 µM. The activation curve of BK Ca channels during exposure to GMQ shifted to a lower depolarized potential, with no change in the gating charge of the curve; however, there was a reduction of free energy for channel activation in its presence. As cells were exposed to GMQ, the amplitude of ion currents were suppressed, including delayed rectifying K + current, voltage-gated Na + and L-type Ca 2+ currents. In Rolf B1.T olfactory sensory neuron, addition of GMQ was able to induce inward current and to suppress peak I Na . Taken together, findings from these results indicated that in addition to the activation of ASIC3 channels, this compound might directly produce additional actions on various types of ion channels. Caution should be taken in the interpretation of in vivo experimental results when GMQ or other structurally similar compounds are used as targets to characterize the potential functions of ASIC3 channels.",
author = "So, {Edmund Cheung} and Yingwei Wang and Yang, {Li Qun} and So, {Kenny Hsu} and Lo, {Yi Ching} and Sheng-Nan Wu",
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T1 - Multiple regulatory actions of 2-guanidine-4-methylquinazoline (GMQ), an agonist of acid-sensing ion channel type 3, on ionic currents in pituitary GH 3 cells and in olfactory sensory (Rolf B1.T) neurons

AU - So, Edmund Cheung

AU - Wang, Yingwei

AU - Yang, Li Qun

AU - So, Kenny Hsu

AU - Lo, Yi Ching

AU - Wu, Sheng-Nan

PY - 2018/5/1

Y1 - 2018/5/1

N2 - GMQ (2-guanidine-4-methylquinazoline or N-(4-methyl-2-quinazolinyl)-guanidine hydrochloride), an agonist of acid-sensing ion channel type 3, has been increasingly used for in vivo studies of alternations in nociceptic behavior. In this study, we tried to investigate whether GMQ has any possible effect on other types of ion channels. Addition of GMQ to pituitary GH3 cells raised the amplitude of Ca 2+ -activated K + currents (I K(Ca) ), which was reversed by verruculogen or PF1022A, but not by TRAM-39. Under inside-out current recordings, addition of GMQ into bath enhanced the probability of large-conductance Ca 2+ -activated K + (BK Ca ) channels with an EC 50 value of 0.95 µM. The activation curve of BK Ca channels during exposure to GMQ shifted to a lower depolarized potential, with no change in the gating charge of the curve; however, there was a reduction of free energy for channel activation in its presence. As cells were exposed to GMQ, the amplitude of ion currents were suppressed, including delayed rectifying K + current, voltage-gated Na + and L-type Ca 2+ currents. In Rolf B1.T olfactory sensory neuron, addition of GMQ was able to induce inward current and to suppress peak I Na . Taken together, findings from these results indicated that in addition to the activation of ASIC3 channels, this compound might directly produce additional actions on various types of ion channels. Caution should be taken in the interpretation of in vivo experimental results when GMQ or other structurally similar compounds are used as targets to characterize the potential functions of ASIC3 channels.

AB - GMQ (2-guanidine-4-methylquinazoline or N-(4-methyl-2-quinazolinyl)-guanidine hydrochloride), an agonist of acid-sensing ion channel type 3, has been increasingly used for in vivo studies of alternations in nociceptic behavior. In this study, we tried to investigate whether GMQ has any possible effect on other types of ion channels. Addition of GMQ to pituitary GH3 cells raised the amplitude of Ca 2+ -activated K + currents (I K(Ca) ), which was reversed by verruculogen or PF1022A, but not by TRAM-39. Under inside-out current recordings, addition of GMQ into bath enhanced the probability of large-conductance Ca 2+ -activated K + (BK Ca ) channels with an EC 50 value of 0.95 µM. The activation curve of BK Ca channels during exposure to GMQ shifted to a lower depolarized potential, with no change in the gating charge of the curve; however, there was a reduction of free energy for channel activation in its presence. As cells were exposed to GMQ, the amplitude of ion currents were suppressed, including delayed rectifying K + current, voltage-gated Na + and L-type Ca 2+ currents. In Rolf B1.T olfactory sensory neuron, addition of GMQ was able to induce inward current and to suppress peak I Na . Taken together, findings from these results indicated that in addition to the activation of ASIC3 channels, this compound might directly produce additional actions on various types of ion channels. Caution should be taken in the interpretation of in vivo experimental results when GMQ or other structurally similar compounds are used as targets to characterize the potential functions of ASIC3 channels.

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