Non-morphogenic effect of Sonic Hedgehog on gastric H+,K+-ATPase activity

Takuto Fujii; Siriporn Phutthatiraphap; Takahiro Shimizu; Hiroshi Takeshima; Hideki Sakai

doi:10.1016/j.bbrc.2019.08.099

Non-morphogenic effect of Sonic Hedgehog on gastric H⁺,K⁺-ATPase activity

Takuto Fujii^*, Siriporn Phutthatiraphap, Takahiro Shimizu, Hiroshi Takeshima, Hideki Sakai

^*Corresponding author for this work

Pharmaceutical Physiology

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

In the stomach, Sonic Hedgehog (Shh) is highly expressed in gastric parietal cells, and acts as a morphogen in early development of the organ. Here, we found that the cleaved N-terminal fragment of Shh (Shh-N) was abundantly expressed in hog gastric vesicles derived from the apical membrane of parietal cells. Interestingly, Shh-N recombinant significantly decreased K⁺-dependent ATP-hydrolyzing activity, which is sensitive to an inhibitor of H⁺,K⁺-ATPase (SCH28080), in hog gastric tubulovesicles and membrane fractions of the H⁺,K⁺-ATPase-expressing cells. In the living cells, Shh-N recombinant inhibited the SCH28080-sensitive ⁸⁶Rb⁺-uptake. Together, Shh-N may directly bind to extracellular side of H⁺,K⁺-ATPase, and negatively regulates the pump activity. This is the first report to explore non-morphogenic property of Shh on ion transporters.

Original language	English
Pages (from-to)	605-609
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	518
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2019.08.099
State	Published - 2019/10/20

Keywords

Gastric acid
H,K-ATPase
Morphogen
Parietal cells
Sonic hedgehog

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2019.08.099

Cite this

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title = "Non-morphogenic effect of Sonic Hedgehog on gastric H+,K+-ATPase activity",

abstract = "In the stomach, Sonic Hedgehog (Shh) is highly expressed in gastric parietal cells, and acts as a morphogen in early development of the organ. Here, we found that the cleaved N-terminal fragment of Shh (Shh-N) was abundantly expressed in hog gastric vesicles derived from the apical membrane of parietal cells. Interestingly, Shh-N recombinant significantly decreased K+-dependent ATP-hydrolyzing activity, which is sensitive to an inhibitor of H+,K+-ATPase (SCH28080), in hog gastric tubulovesicles and membrane fractions of the H+,K+-ATPase-expressing cells. In the living cells, Shh-N recombinant inhibited the SCH28080-sensitive 86Rb+-uptake. Together, Shh-N may directly bind to extracellular side of H+,K+-ATPase, and negatively regulates the pump activity. This is the first report to explore non-morphogenic property of Shh on ion transporters.",

keywords = "Gastric acid, H,K-ATPase, Morphogen, Parietal cells, Sonic hedgehog",

author = "Takuto Fujii and Siriporn Phutthatiraphap and Takahiro Shimizu and Hiroshi Takeshima and Hideki Sakai",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

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T1 - Non-morphogenic effect of Sonic Hedgehog on gastric H+,K+-ATPase activity

AU - Fujii, Takuto

AU - Phutthatiraphap, Siriporn

AU - Shimizu, Takahiro

AU - Takeshima, Hiroshi

AU - Sakai, Hideki

PY - 2019/10/20

Y1 - 2019/10/20

N2 - In the stomach, Sonic Hedgehog (Shh) is highly expressed in gastric parietal cells, and acts as a morphogen in early development of the organ. Here, we found that the cleaved N-terminal fragment of Shh (Shh-N) was abundantly expressed in hog gastric vesicles derived from the apical membrane of parietal cells. Interestingly, Shh-N recombinant significantly decreased K+-dependent ATP-hydrolyzing activity, which is sensitive to an inhibitor of H+,K+-ATPase (SCH28080), in hog gastric tubulovesicles and membrane fractions of the H+,K+-ATPase-expressing cells. In the living cells, Shh-N recombinant inhibited the SCH28080-sensitive 86Rb+-uptake. Together, Shh-N may directly bind to extracellular side of H+,K+-ATPase, and negatively regulates the pump activity. This is the first report to explore non-morphogenic property of Shh on ion transporters.

AB - In the stomach, Sonic Hedgehog (Shh) is highly expressed in gastric parietal cells, and acts as a morphogen in early development of the organ. Here, we found that the cleaved N-terminal fragment of Shh (Shh-N) was abundantly expressed in hog gastric vesicles derived from the apical membrane of parietal cells. Interestingly, Shh-N recombinant significantly decreased K+-dependent ATP-hydrolyzing activity, which is sensitive to an inhibitor of H+,K+-ATPase (SCH28080), in hog gastric tubulovesicles and membrane fractions of the H+,K+-ATPase-expressing cells. In the living cells, Shh-N recombinant inhibited the SCH28080-sensitive 86Rb+-uptake. Together, Shh-N may directly bind to extracellular side of H+,K+-ATPase, and negatively regulates the pump activity. This is the first report to explore non-morphogenic property of Shh on ion transporters.

KW - Gastric acid

KW - H,K-ATPase

KW - Morphogen

KW - Parietal cells

KW - Sonic hedgehog

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