Inhibition of acid formation by epidermal growth factor in the isolated rabbit gastric glands.
The effects of epidermal growth factor (EGF) on basal and stimulated (with histamine, dibutyryl cyclic AMP, and high concentrations of K+) acid formation have been studied in isolated glands from the rabbit gastric mucosa. The changes in the accumulation of [14C]aminopyrine [14C]AP have been used as an indirect measurement of acid production in the glands. Unstimulated gastric glands accumulated [14C]AP indicating the existence of basal acid production in these glands, and EGF caused a small but significant reduction in basal [14C]AP uptake. A similar reduction of basal [14C]AP uptake was observed after exposure to omeprazole but not after ranitidine or prostaglandin E2 (PGE2). Histamine, dibutyryl cyclic AMP and K+ caused a strong and dose-dependent stimulation of acid formation by the glands. EGF, like omeprazole, reduced dose-dependently the [14C]AP accumulation stimulated by both histamine and dibutyryl cyclic AMP, while ranitidine and PGE2 reduced histamine- but not dibutyryl-cyclic-AMP-stimulated accumulation of [14C]AP. In the absence of other external stimuli, an increased K+ concentration enhanced [14C]AP accumulation to levels similar to those produced by histamine and this effect was not changed by EGF, ranitidine or PGE2 but was inhibited by omeprazole. We conclude that EGF interferes with the final steps of acid production between cyclic nucleotides and proton pump of the parietal cells.
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003864:Depression, Chemical; D015232:Dinoprostone; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D011817:Rabbits; D011899:Ranitidine / Q000494:pharmacology
D011458:Prostaglandins E; D000632:Aminopyrine; D004815:Epidermal Growth Factor; D003994:Bucladesine; D006632:Histamine; D011899:Ranitidine; D015232:Dinoprostone; D009853:Omeprazole; D011188:Potassium