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Molecular Pharmacology

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Research ArticleArticle

Activation of Inositol 1,4,5-Trisphosphate Receptor Is Essential for the Opening of Mouse TRP5 Channels

Hideaki Kanki, Mariko Kinoshita, Akinori Akaike, Masamichi Satoh, Yasuo Mori and Shuji Kaneko
Molecular Pharmacology November 2001, 60 (5) 989-998; DOI: https://doi.org/10.1124/mol.60.5.989
Hideaki Kanki
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Mariko Kinoshita
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Akinori Akaike
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Masamichi Satoh
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Yasuo Mori
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Shuji Kaneko
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Abstract

We studied the opening mechanism of Ca2+-permeable channels formed with mouse transient receptor potential type 5 (mTRP5) usingXenopus oocytes. After stimulation of coexpressed muscarinic M1 receptors with acetylcholine (ACh) in a Ca2+-free solution, switching to 2 mM Ca2+-containing solution evoked a large Cl−current, which reflects the opening of endogenous Ca2+-dependent Cl− channels following Ca2+ entry through the expressed channels. The ACh-evoked response was not affected by a depletion of Ca2+ store with thapsigargin but was inhibited by preinjection of antisense oligodeoxynucleotides (ODNs) to Gq, G11, or both. The mTRP5 channel response was also induced by a direct activation of G proteins with injection of guanosine 5′-3-O-(thio)triphosphate (GTPγS). The ACh- and GTPγS-evoked responses were inhibited by either pretreatment with a phospholipase C inhibitor, U73122, or an inositol-1,4,5-trisphosphate (IP3) receptor inhibitor, xestospongin C (XeC). An activation of IP3 receptors with injection of adenophostin A (AdA) evoked the mTRP5 channel response in a dose-dependent manner. The AdA-evoked response was not suppressed by preinjection of antisense ODNs to Gq/11 or U73122 but was suppressed by either preinjection of XeC or a peptide mimicking the IP3 binding domain of Xenopus IP3 receptor. These findings suggest that the activation of IP3 receptor is essential for the opening of mTRP5 channels, and that neither G proteins, phosphoinositide metabolism, nor depletion of the Ca2+ store directly modifies the IP3receptor-linked opening of mTRP5 channels.

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Molecular Pharmacology: 60 (5)
Molecular Pharmacology
Vol. 60, Issue 5
1 Nov 2001
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Research ArticleArticle

Activation of Inositol 1,4,5-Trisphosphate Receptor Is Essential for the Opening of Mouse TRP5 Channels

Hideaki Kanki, Mariko Kinoshita, Akinori Akaike, Masamichi Satoh, Yasuo Mori and Shuji Kaneko
Molecular Pharmacology November 1, 2001, 60 (5) 989-998; DOI: https://doi.org/10.1124/mol.60.5.989

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Research ArticleArticle

Activation of Inositol 1,4,5-Trisphosphate Receptor Is Essential for the Opening of Mouse TRP5 Channels

Hideaki Kanki, Mariko Kinoshita, Akinori Akaike, Masamichi Satoh, Yasuo Mori and Shuji Kaneko
Molecular Pharmacology November 1, 2001, 60 (5) 989-998; DOI: https://doi.org/10.1124/mol.60.5.989
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