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Inhibition of Parietal Cell Acid Secretion Is Mediated by the Classical Epidermal Growth Factor Receptor

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Abstract

Epidermal growth factor (EGF) and transforminggrowth factor-α (TGF-α) inhibit gastric acidsecretion both in vivo and in vitro. Previous studieshave indicated that EGF and TGF-α bind to the same EGF/TGF-α receptor. Nevertheless, weand others have previously demonstrated that inhibitionof acid secretion by these growth factors requiresconcentrations of the peptides that are 10-fold higher than those necessary for induction ofmitogenesis. Therefore, we have sought to investigatewhether gastric parietal cells may possess a secondEGF/TGF-α receptor class. Two systems werestudied: First, [125I]TGF-α was cross-linkedto the receptor in isolated rabbit parietal cellmembranes, and labeled species were resolved onSDS-PAGE. Second, acid secretion was evaluated inpylorus-ligated waved-2 mutant mice, which carry a disabling pointmutation in their classical EGF/TGF-α receptor. Inisolated parietal cells, [125I]TGF-αwas cross-linked into a single species of 170 kDa.Cross-linking was inhibited in the presence of unlabeledTGF-α with an IC of 80 nM. In the pylorus-ligatedmice, control littermate mice demonstrated adose-dependent inhibition of acid secretion by EGF withan IC of 20 μg/kg. In contrast, EGF had noinhibitory effect on acid secretion in 50 waved-2 miceat concentrations up to 100 μg/kg. No alterations inparietal cell or gastrin cell numbers were observed.These results in both isolated rabbit parietal cellsand waved-2 mice support the existence of only a singleclass of EGF/TGF-α receptors in parietal cells.Differences in growth factor affinity are likely due to the modification of the receptor or oneof its coordinate regulators.

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Authors
  1. Virendra Joshi
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  2. Gregory S. Ray
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  3. James R. Goldenring
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Joshi, V., Ray, G.S. & Goldenring, J.R. Inhibition of Parietal Cell Acid Secretion Is Mediated by the Classical Epidermal Growth Factor Receptor. Dig Dis Sci 42, 1194–1198 (1997). https://doi.org/10.1023/A:1018845805806

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