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.
| Original language | English |
|---|---|
| Pages (from-to) | 79-88 |
| Number of pages | 10 |
| Journal | Biochemical Pharmacology |
| Volume | 151 |
| DOIs | |
| Publication status | Published - 2018 May 1 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Pharmacology
Cite this
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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 . / So, Edmund Cheung; Wang, Yingwei; Yang, Li Qun; So, Kenny Hsu; Lo, Yi Ching; Wu, Sheng-Nan.
In: Biochemical Pharmacology, Vol. 151, 01.05.2018, p. 79-88.Research output: Contribution to journal › Article
TY - JOUR
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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U2 - 10.1016/j.bcp.2018.02.027
DO - 10.1016/j.bcp.2018.02.027
M3 - Article
VL - 151
SP - 79
EP - 88
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
ER -