The site and mechanism of action of epidermal growth factor (EGF) on acid secretion by rat isolated parietal cells were investigated by using the intracellular accumulation of the weak base aminopyrine as an index of secretory activity. When parietal cells were stimulated with histamine (0.5 mM), the concentration of EGF required for half-maximal inhibition of acid secretion was 19 nM, with a maximally effective concentration of EGF producing 38% inhibition of secretory activity. EGF did not inhibit secretion stimulated by 0.1 mM-carbachol, or by 30 microM-, 56 microM-, 100 microM- or 1000 microM-dibutyryl cyclic AMP, low concentrations of which produced a secretory response comparable with that obtained with 0.5 mM-histamine. Addition of 0.1 mM-3-isobutyl-1-methylxanthine (IBMX) substantially increased aminopyrine accumulation in the presence of 0.5 mM-histamine. The inhibitory action of EGF on histamine-stimulated secretion was blocked by 0.1 mM-IBMX, even if low concentrations of histamine were used to generate aminopyrine accumulation ratios similar to those obtained with 0.5 mM-histamine alone. The cyclo-oxygenase inhibitor flurbiprofen (1-100 microM) and the cyclo-oxygenase and lipoxygenase inhibitor nordihydroguaiaretic acid (10-100 microM) did not affect the inhibitory action of EGF. The pattern of inhibition of secretion produced by the activator of Ca2+-sensitive phospholipid-dependent protein kinase, 12-O-tetradecanoylphorbol 13-acetate, was markedly different from that produced by EGF. In conclusion, a major site of the action of EGF on acid secretion in the intact stomach is probably a decrease in the stimulatory effect of histamine by a mechanism which does not involve Ca2+-sensitive phospholipid-dependent protein kinase or the production of prostaglandins, but which might involve enhancement of cyclic AMP phosphodiesterase activity.
Skip Nav Destination
Article navigation
June 1987
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkAdvertising
Research Article|
June 15 1987
Action of epidermal growth factor on acid secretion by rat isolated parietal cells
G P Shaw;
G P Shaw
1Department of Molecular Sciences, Aston University, Birmingham, U.K.
Search for other works by this author on:
J F Hatt;
J F Hatt
1Department of Molecular Sciences, Aston University, Birmingham, U.K.
Search for other works by this author on:
N G Anderson;
N G Anderson
1Department of Molecular Sciences, Aston University, Birmingham, U.K.
Search for other works by this author on:
P J Hanson
P J Hanson
1Department of Molecular Sciences, Aston University, Birmingham, U.K.
Search for other works by this author on:
Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1987 London: The Biochemical Society
1987
Biochem J (1987) 244 (3): 699–704.
Citation
G P Shaw, J F Hatt, N G Anderson, P J Hanson; Action of epidermal growth factor on acid secretion by rat isolated parietal cells. Biochem J 15 June 1987; 244 (3): 699–704. doi: https://doi.org/10.1042/bj2440699
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.