gastrins and pimagedine

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.

Topics: Amine Oxidase (Copper-Containing); Animals; Ceruletide; Female; gamma-Aminobutyric Acid; Gastric Mucosa; Gastrins; Guanidines; Male; Putrescine; Rats; Rats, Inbred Lew

We attempted to elucidate the factors involved in gastric hypersecretion of rats during pregnancy and lactation. Acid secretion in pylorus-ligated and vagally denervated fistula rats stimulated with histamine, tetragastrin, and methacholine increased from midterm pregnancy and persisted during lactation. Pepsin secretion remained unaltered during pregnancy but increased during lactation. Vagal denervation itself abolished this hypersecretion. In late pregnancy, a delayed appearance of maximal acid response to histamine was apparent, as compared to nonpregnant rats, and was abolished by aminoguanidine treatment. There was a delay in the maximal response to tetragastrin but not to methacholine. Serum histamine concentrations were 3-4 times higher in late pregnancy, as compared to nonpregnant, lactating and nonlactating rats. Gastric DNA and protein concentrations were significantly increased in lactating rats with concomitant elevation of food intake and serum gastrin levels. Those changes disappeared in nonlactating rats, and gastric secretion was much the same in the nonpregnant rats. These results indicate that acid hypersecretion during pregnancy was exclusively associated with vagal innervation plus high serum histamine levels, while acid and pepsin hypersecretion in lactating rats were associated with vagal innervation plus hyperplastic gastric mucosa and high serum gastrin levels.

Topics: Animals; DNA; Female; Gastric Acid; Gastric Juice; Gastric Mucosa; Gastrins; Guanidines; Histamine; Lactation; Male; Methacholine Chloride; Methacholine Compounds; Nucleic Acids; Pepsin A; Pregnancy; Pregnancy, Animal; Proteins; Rats; Tetragastrin; Time Factors

A method is described for the partial purification of hog's antral gastrin by gel filtration and ion-exchange chromatography. Gastrin was assayed by its effect on the pH of the effluent fluid from the perfused lumen of the stomach of the anaesthetized rat. The latency of the response to gastrin given intravenously was shorter than the latency to a similar dose of histamine. The response to gastrin injected into the arterial circulation of the stomach appeared sooner than the response to gastrin injected intravenously. Iproniazid and aminoguanidine potentiated responses to gastrin. Incubation in vitro with monamine oxidase or diamine oxidase did not inactivate gastrin. Chlorpromazine and bromolysergic acid diethylamide, in doses which enhance the effects of histamine on acid gastric secretion, did not affect responses to gastrin.

Topics: Administration, Intravenous; Amine Oxidase (Copper-Containing); Animals; Biological Assay; Chlorpromazine; Chromatography; Chromatography, Gel; Chromatography, Ion Exchange; Gastric Acidity Determination; Gastrins; Guanidine; Guanidines; Histamine; Injections; Injections, Intravenous; Iproniazid; Lysergic Acid Diethylamide; Monoamine Oxidase; Pharmacology; Rats; Research; Stomach; Swine