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Histamine induces sonic hedgehog secretion across the apical membrane of polarized parietal cells
Author(s) -
Zavros Yana,
Orr Melissa A.,
Malinowska Danuta H.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.938.3
Subject(s) - sonic hedgehog , parietal cell , secretion , foveolar cell , apical membrane , gastric glands , microbiology and biotechnology , biology , enterochromaffin like cell , histamine , chemistry , gastric acid , biochemistry , endocrinology , membrane , gastric mucosa , stomach , signal transduction
Objective: Sonic Hedgehog (Shh) is processed and secreted from parietal cells by a unique acid‐ and protease‐dependent mechanism ( Zavros et al., 2007, JBC ). The current study seeks to determine the cellular location of Shh within the gastric parietal cell. Methods: Shh expression was studied using cimetidine (resting) or histamine (stimulated)‐treated rabbit gastric glands and immunoisolated tubulovesicles. Apical (AP) and basolateral (BL) Shh secretion was studied using polarized human gastric cancer cells (23132/87). Results: Confocal microscopy of gastric glands triple stained for Shh, H + ,K + ‐ATPase and zymogen or neck cell markers showed expression of Shh within the canaliculus of stimulated parietal cells. Western blots showed Shh and H + ,K + ‐ATPase expression in resting immunoisolated tubulovesicles. While the Shh precursor was detected in resting membranes, increased expression of processed Shh was observed in stimulated tubulovesicles. Surface biotinylation of polarized 23132/87 cells revealed expression of the Shh precursor at the AP membrane and processed Shh secreted in the AP media. Shh was not detected in either the BL biotinylated membrane lysates or media. Conclusion: Shh is expressed in H + ,K + ‐ATPase‐containing membranes suggesting that processing and secretion occurs across the apical membrane of parietal cells.