Gastrin stimulation of histamine synthesis in enterochromaffin-like
cells from rabbit fundic mucosa.
Hollande, Fr[acute]ed[acute]eric, Sonia Combettes, Jean-Pierre Bali,
and Richard Magous.
Laboratoire de Biochimie des Membranes, CJF INSERM 92-07,
Facult[acute]e de Pharmacie, 15, av. Charles Flahault, 34060
MONTPELLIER CEDEX (France)
APStracts 2:0209G, 1995.
This work aimed to investigate the molecular role of gastrin in
histamine synthesis in isolated rabbit fundic mucosal cells enriched
in enterochromaffin-like (ECL) cells (37%). Gastrin stimulated
histidine decarboxylase activity (HDC) by increasing the Vmax from
0.240+/-0.017 (basal value) to 0.332+/-0.012 pmol.mg protein-1.h-1
and by decreasing the Km (73.90+/-2.2 [mu]M vs 93.42+/-4.32 [mu]M
(basal value)). Pertussis toxin (PTX) (200 ng/ml) reduced from 41.8%
to 15.9% the stimulation of HDC induced by 10 nM gastrin, whereas
cholera toxin (CTX) (100 ng/ml) was without effect. Staurosporin and
polymyxin B inhibited in a dose-dependent manner the HDC activity
stimulated by 10 nM gastrin. Phorbol-12 myristate-13 acetate (PMA)
(100 nM) decreased Vmax (0.558+/-0.021 pmol.mg protein-1.h-1) but did
not change the Km. Furthermore, cycloheximide (0.1 [mu]M to 10 [mu]M)
inhibited the gastrin-induced stimulation of HDC activity, whereas
actinomycin D (up to 10 [mu]M) was without effect. Finally,
incubation of cells with gastrin (10 nM) left the expression of HDC
mRNA unchanged. We concluded that gastrin, acting through
"gastrin/CCK-B type" receptors coupled to PTX-sensitive G
protein, regulate histamine synthesis in gastric ECL cells by
increasing both the affinity of HDC for L-histidine and the number of
active enzyme molecules. This last event, related to protein kinase C
(PKC) activation, could be due to a translational or post
translational mechanism.
Received 12 December 1994; accepted in final form 27 September
1995.
APS Manuscript Number G482-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95