Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The polyamines spermidine and spermine are essential for cell proliferation. Most growth factors stimulate polyamine synthesis by inducing ornithine decarboxylase activity, which catalyzes the formation of putrescine from ornithine. Putrescine can then be utilized either for polyamine biosynthesis or may serve as a substrate for diamine oxidase (DAO), leading to formation of gamma-aminobutyric acid (GABA). Growth of the oxyntic mucosa of the stomach is stimulated by feeding, by trophic hormones such as gastrin and by exogenous administration of putrescine. Conversely, fasting, as well as ornithine decarboxylase inhibition decrease oxyntic mucosal DNA synthesis. We now demonstrate that fasted rats show a high degree of [3H]GABA formation from [3H]putrescine in the oxyntic mucosa and that feeding or injections of gastrin, caerulein or the DAO-inhibitor aminoguanidine decrease such [3H]GABA formation and, instead, stimulate formation of [3H]spermidine. Moreover, gastrin injections reduced oxyntic mucosal DAO activity. Thus, oxyntic mucosal DAO activity is regulated by tropic factors and may be involved in growth regulation by controlling intramucosal putrescine metabolism.
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PMID:Regulation of gastric mucosal diamine oxidase activity by gastrin. 164 66

Trophic changes of the exocrine pancreas after in vivo gastrin (G)/CCK treatment are well documented but up to now the study of the mechanisms involved is restricted by the lack of a suitable in vitro model. Nevertheless the in vivo trophic effect induced by gastrin/CCK peptides has been associated with an increase of ornithine decarboxylase (ODC) activity. In the present work, using the AR42J cell line in which CCK receptors and stimulation of amylase release by CCK peptides has already been demonstrated, we investigated the presence of gastrin binding sites and the possible modulation of proliferation by an inhibitor of ODC activity. 125I-BH-G17ns binding is saturable, reversible and specific. Potencies of the different analogues tested are G17ns greater than CCK8 greater than CCK8ns greater than or equal to G6s greater than G/CCK4. Furthermore dBt cGMP, a non-peptide antagonist for CCK receptors, does not compete for gastrin binding. This indicates the existence of a subclass of gastrin binding sites. Difluoromethyl ornithine (DFMO) (1 mM), an irreversible inhibitor of ODC, inhibits cell growth from day 3 up to day 7. This growth inhibition is dose dependent and closely related to an intracellular polyamine modulation. Putrescine and spermidine levels fell under detectable values while spermine levels increased. All these data suggest that this cell line could be a useful in vitro model to study the mechanisms of gastrin induced growth control.
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PMID:Characterisation of gastrin receptors on a rat pancreatic acinar cell line (AR42J). A possible model for studying gastrin mediated cell growth and proliferation. 312 56

Either ethylamine or the diamine putrescine was infused at the rate of 1 mumol/h for 66 h into the ileal lumen of rats. Total mucosal RNA, DNA, and protein content was greater in amine-treated rats than in rats receiving 0.9% NaCl. Growth was greatest in the mucosa surrounding the tip of the infusion catheter but was also observed 9 cm proximal and distal to the catheter tip. Infusion of these amines induced the activity of the enzymes ornithine and S-adenosylmethionine decarboxylase. Ornithine decarboxylase activity was increased 2- and 6-fold and S-adenosylmethionine decarboxylase activity 10- and 5-fold by putrescine and ethylamine, respectively. Induction of the polyamine biosynthetic enzymes was not accompanied by increases in the tissue content of polyamines. Putrescine, spermidine, and spermine content of the ileal mucosa surrounding the catheter tip was the same in 0.9% NaCl-, ethylamine-, and putrescine-treated animals. Finally, ethylamine was without effect on serum gastrin concentration in these experiments. The results suggest that amines regulate mucosal growth and may do so by modulating the activity of the enzymes involved in the synthesis of the polyamines.
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PMID:Ileal mucosal growth during intraluminal infusion of ethylamine or putrescine. 405 Sep 94